Biomedical subjects

C Crone

Publications and source records attributed to C Crone.

At least 37 records · Page 2Linked to original sources

PubMed1993

Reciprocal inhibition in man.

Reciprocal inhibition is the automatic antagonist alpha motor neurone inhibition which is evoked by contraction of the agonist muscle. This so-called natural reciprocal inhibition is a ubiquitous and pronounced phenomenon in man and must be suspected of playing a major role in the control of voluntary movements. The spinal pathways underlying this inhibitory phenomenon were studied. The disynaptic reciprocal Ia inhibitory pathway between the tibial anterior muscle and the soleus alpha motor neurones was identified and described in man. It was shown that the inhibition can be evoked in most healthy subjects at rest, but the degree of inhibition varies considerably from one subject to another. It was concluded that it corresponds to the disynaptic reciprocal Ia inhibitory pathway which has been extensively described in animal experiments. The disynaptic reciprocal inhibition was shown to increase during the dynamic phase of a dorsiflexion movement of the foot, but not during the tonic phase. However, when the peripheral afferent feedback from the contracting muscle was blocked by ischaemia, an increase of the inhibition was revealed also during the tonic phase of the dorsiflexion. The concealment of this increase during unrestrained peripheral feedback from the muscle was thought to be due to the post-activation depression mechanism; a mechanism which was described further and which probably involves reduced transmitter release at Ia afferent terminals as a result of previous activation of these afferent fibers. Hence the hypothesis was supported that alpha motor neurones and the corresponding inhibitory interneurones, which project reciprocal inhibition to the antagonist motor neurones, are activated in parallel during voluntary contraction of agonist muscles. An additional reciprocal inhibitory mechanism, the long latency reciprocal inhibition, was described between the tibial anterior muscle and the soleus alpha motor neurones. It was shown to be evoked by group I afferent activity and it was seen at a conditioning-test interval of 3-6 msec. It was initiated by supraspinal pathways and it was seen only during dorsiflexion of the foot. The pathway underlying this inhibitory mechanism is unknown, but it was suggested that it was mediated by a propriospinal pathway. The possible contribution to reciprocal inhibition of presynaptic inhibition of soleus Ia afferent fibers was studied by an indirect method. It was concluded that this presynaptic inhibition was increased during even slight dorsiflexion of the foot and that the increase was mainly dependent upon the peripheral afferent input from the contracting muscle.(ABSTRACT TRUNCATED AT 400 WORDS)

Humans↗

PubMed1992

Central facilitation of Ia inhibition during tonic ankle dorsiflexion revealed after blockade of peripheral feedback.

Recent studies have reported that no increase of the disynaptic reciprocal inhibition can be observed during tonic voluntary dorsiflexion of the foot as compared to rest, when the size of the control H-reflex is kept constant. Other studies have, however, shown that a voluntary contraction evokes a strong and long-lasting depression of the synaptic transmission from Ia afferents to motoneurones, most likely secondary to activation of these afferents during the contraction (post-activation depression). It was thought that this effect could also interfere with the demonstration of a central facilitation of the reciprocal inhibition during movement. The amount of disynaptic Ia reciprocal inhibition from the pretibial flexors to the soleus H-reflex was therefore estimated in normal human subjects at rest and during voluntary tonic dorsiflexion before, during and after blocking the peripheral feedback from the investigated muscles. It was observed that the reciprocal inhibition measured during dorsiflexion increased during occlusion of the blood supply to the leg, reaching a maximum of inhibition after 30 min of ischaemia. After release of the ischaemia the inhibition gradually decreased to its pre-ischaemic level. It is therefore suggested that the brain facilitates transmission in the Ia disynaptic reciprocal pathway during tonic voluntary dorsiflexion of the foot, but that this facilitation is normally not observed due to a post-activation depression following the peripheral feedback activation during the movement.

Adult↗

PubMed1990

Sensitivity of monosynaptic test reflexes to facilitation and inhibition as a function of the test reflex size: a study in man and the cat.

In parallel experiments on humans and in the cat it was investigated how the sensitivity of monosynaptic test reflexes to facilitation and inhibition varies as a function of the size of the control test reflex itself. In man the monosynaptic reflex (the Hoffmann reflex) was evoked in either the soleus muscle (by stimulation of the tibial nerve) or the quadriceps muscle (by stimulation of the femoral nerve). In the decerebrate cat monosynaptic reflexes were recorded from the nerves to soleus and medial gastrocnemius muscles; they were evoked by stimulation of the proximal ends of the sectioned L7 and S1 dorsal roots. Various excitatory and inhibitory spinal reflex pathways were used for conditioning the test reflexes (e.g. monosynaptic Ia excitation, disynaptic reciprocal inhibition, cutaneous inhibition, recurrent inhibition, presynaptic inhibition of the Ia fibres mediating the test reflex). It was shown that the additional number of motoneurones recruited in a monosynaptic test reflex by a constant excitatory conditioning stimulus was very much dependent on the size of the test reflex itself. This dependency had the same characteristic pattern whatever the conditioning stimulus. With increasing size of the test reflex the number of additionally recruited motoneurones first increased, then reached a peak (or plateau) and finally decreased. A similar relation was also seen with inhibitory conditioning stimuli. The basic physiological factors responsible for these findings are discussed. Finally, the implications for the interpretation of experiments in man with the H-reflex technique are considered.

Adolescent↗

PubMed1989

Methodological implications of the post activation depression of the soleus H-reflex in man.

A long lasting inhibition (greater than 8 s) of the soleus Hoffmann reflex (H-reflex) was evoked by a preceding soleus H-reflex, by a brief voluntary ankle flexor or extensor muscle contraction or by a tap applied to the Achilles tendon. The time course of this long lasting inhibition was similar in all these cases, suggesting that the same spinal mechanism is involved. Furthermore, it was shown that the post-activation depression may interfere with the determination of inhibitory or facilitatory effects on the H-reflex. It is stressed that when the onset of inhibitory or facilitatory effects on the soleus H-reflex is to be determined in relation to start of an ankle movement, either very long stimulus intervals (greater than 8 s) must be used, or the onset must be determined in relation to a reference value of the soleus H-reflex, which may be influenced by the long lasting inhibitory effect, but not yet by the succeeding muscle contraction.

Adult↗

PubMed1989

Growth of colorectal carcinoma cells: regulation in vitro by gastrin, pentagastrin and the gastrin-receptor antagonist proglumide.

The growth-regulating effects of pentagastrin, gastrin and the gastrin-receptor antagonist proglumide were investigated in three established cell lines derived from human colorectal carcinomas in vitro and after transplantation into nude mice. In vitro a significant increase of cell growth in the SW 403 cell line incubated with pentagastrin or gastrin was observed. In the Lovo cell line this effect was only detected after synchronization of cell growth. Pentagastrin and gastrin had no effect on the growth of the Ls 174 T cell line. Proglumide reduced cell proliferation in all three cell lines as well as in the L929S cell line derived from fibroblasts, which served as control. After transplantation into nude mice all tumor cell lines increased, Lovo and Ls 174 T as undifferentiated tumor, SW 403 as differentiated. Pentagastrin increased and proglumide decreased growth in SW 403 tumors, whereas no effect was observed on Ls 174 T and Lovo tumors. We therefore conclude that growth of some colorectal carcinomas is regulated by gastrin, but that the effect of proglumide is unspecific rather than related to blockage of gastrin receptors. The growth-regulating effect of gastrin could be due to tumor differentiation.

Animals↗

PubMed1989

Cellular effects of beta-adrenergic and of cAMP stimulation on potassium transport in rat alveolar epithelium.

Alveolar fluid absorption is greatly enhanced by cAMP and by beta-adrenergic agonists via an increase in Na+ transport. Little is known about K+ homeostasis under these circumstances. We studied K+ transport across alveolar epithelium in isolated perfused rat lungs stimulated either by dibutyryl-cAMP or isoproterenol. K+ fluxes and the apparent permeability of 86Rb across the epithelium (alveoli to plasma) were interpreted according to a model involving two types of cells, B and L, distinguished by the location of Na+-K+-ATPases (basal and luminal). Water is considered to be absorbed by B cells in a solute-coupled process energized by a basolateral Na+-K+-ATPase that is stimulated by isoproterenol and cAMP. K+ transport out of the alveoli is due to the activity of a Na+-K+-ATPase located in the apical membrane of L cells. In the present study net transport rate of K+ was -0.5 +/- 0.15 nmol/s, n = 20 (out of alveoli) in control conditions. When the epithelium was stimulated by dibutyryl-cAMP (10(-4) mol/l) net absorption of K+ reversed to net 'secretion' into alveoli (3.2 +/- 0.31 nmol/s), fluid absorption was not stimulated. K+ 'secretion' was abolished by apical Ba2+, indicating it was due to opening of apical K+ channels. Basolateral ouabain reversed net K+ 'secretion' to net absorption indicating that K+ entry into alveoli was dependent on activity of B cell basolateral Na+-K+-ATPase (masking simultaneous K+ removal by apical L cell Na+-K+-pump). When larger concentrations of dibutyryl-cAMP (10(-3) mol/l) or when isoproterenol were used to stimulate the epithelium there was a tripling of fluid absorption.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Agonists↗

PubMed1989

Spinal mechanisms in man contributing to reciprocal inhibition during voluntary dorsiflexion of the foot.

1. The inhibition of the soleus Hoffmann reflex (H reflex) during voluntary dorsiflexion of the foot--henceforth referred to as 'natural' reciprocal inhibition--was found to be initiated 50 ms before the onset of the EMG activity in the tibialis anterior muscle and to increase gradually during a ramp-and-hold dorsiflexion. There was a positive correlation between strength of tonic dorsiflexion and amount of 'natural' reciprocal inhibition. 2. The change of activity in the disynaptic and a long-latency group Ia inhibitory pathway and the change in presynaptic inhibition of the Ia fibres mediating the soleus H reflex were tested separately during ramp-and-hold dorsiflexion as well as during tonic dorsiflexion of the foot, and the results were compared with the development of the 'natural' reciprocal inhibition of the unconditioned soleus H reflex. 3. The disynaptic group I inhibition of soleus motoneurones was increased, as compared to rest, during the dynamic phase of a ramp-and-hold dorsiflexion movement, but the inhibition generally did not increase during tonic dorsiflexion of the foot. 4. The long-latency group I inhibition was seen only during dorsiflexion of the foot. It appeared around 50 ms before tibial anterior EMG activity and there was a positive correlation between strength of tonic dorsiflexion and amount of this long-latency inhibition. 5. Presynaptic inhibition of Ia afferents terminating on soleus motoneurones was estimated by an indirect method. The increase of presynaptic inhibition started soon after the onset of the ramp-and-hold dorsiflexion, and gradually became more pronounced during the ramp phase. The amount of presynaptic inhibition was positively correlated with strength of tonic dorsiflexion. 6. It is concluded that all investigated mechanisms may contribute to the 'natural' reciprocal inhibition and it seems that the different pathways are used differentially during different types of movement.

Adult↗

PubMed1989

Presynaptic modulation of sympathetic nerve transmission--an element in vasomotor control.

We have earlier presented evidence that adenosine may create vasodilation via presynaptic inhibition of sympathetic nerve fibers to muscle arterioles. In the present study the effect of selective adenosine antagonists on arteriolar diameter was investigated, using an autoperfused frog muscle (m. cutaneus pectoris). During application of the antagonists arteriolar diameter reductions were observed in the transparent, transilluminated muscle. The sulfonylated xanthine derivatives 8-(p-sulfo)phenyltheophylline (8-PS phi T), 8-(m-sulfo)phenyltheophylline (8-MS phi T) and 1,3-dipropyl-8-p-sulfonphenylxanthine (DPSPX) are all considered to be selective competitive adenosine antagonists without unspecific intracellular effects. Topical application of each of these compouns on resting muscle resulted in a dose-dependent arteriolar contraction. The constriction was immediately reversed by addition of the adrenergic alpha-receptor blocker phentolamine (7.1 x 10(-5) M), indicating that the arteriolar contraction was due to activation of postjunctional alpha-receptors present in vascular smooth muscle. Also, the A1-selective adenosine agonist (-)-N6-(R-phenylisopropyl)-adenosine (R-PIA) eliminated the arteriolar constriction. These effects suggest, that the xanthine derivatives release the sympathetic nerve terminals from inhibition by endogenous adenosine. When nerve fibers were blocked by tetrodotoxin (TTX), 3 x 10(-6)M or when the frogs had been chemically sympathectomized with 6-hydroxydopamine (6-OHDA), no significant arteriolar contraction was observed during adenosine antagonist administration, complying with the view that in resting muscle endogenous adenosine acts presynaptically to inhibit sympathetic nerve terminals. These results suggest that presynaptic adenosine effects are not only involved in regulation of frog skeletal muscle blood flow in response to activity, but also play a role in the control of arteriolar tone in resting muscle.

Adenosine↗

PubMed1988

Apical sodium-sugar transport in pulmonary epithelium in situ.

The presence of an apical sodium-coupled transport system for D-glucose in lung alveolar epithelial cells has been demonstrated in lungs instilled with Ringer's fluid and perfused with either blood or Ringer's fluid (Basset et al. (1987) J. Physiol. 384, 325-345). The direction of transport is from alveoli towards interstitium. The characteristics of the system were evaluated in similar preparations by use of sugar analogues such as alpha-methyl-glucopyranoside, 2-deoxyglucose, 3-O-methylglucose and L-glucose. The main finding was the presence of a transport system for alpha-methylglucopyranoside and 2-deoxyglucose in the apical cell membrane. This system was unaffected by phloretin. Both alpha-methylglucopyranoside and 2-deoxyglucose transports were inhibited by phloridzin and by the presence of glucose (10(-2) mol.l-1). Competition was demonstrated between D-glucose and alpha-methylglucopyranoside or 2-deoxyglucose, but not for 3-O-methylglucose or L-glucose. 3-O-Methylglucose was cleared as slowly as L-glucose. The results comply partly with those known from intestinal epithelium and kidney proximal tubular epithelium, but the handling of 3-O-methylglucose was different. The relative transport rates of Na+ and glucose are compatible with a Na+: glucose coupling ratio larger than one.

Animals↗

PubMed1988

Potassium transport across rat alveolar epithelium: evidence for an apical Na+-K+ pump.

1. Experiments were performed on rat lungs into which various solutions were instilled whilst the lungs were perfused with either whole blood or Ringer solution. Instillation of ion-free glucose solution led to a net flux of fluid and ions into the alveolar spaces. K+ ions entered faster than Na+ ions and reached a concentration about twice that in the perfusate. Ouabain in the perfusate (basolateral side) prevented the rise in alveolar K+ concentration above that in the perfusate, indicating a transcellular pathway. Ba2+ in the instillate (apical side) hindered the entry of K+ into alveoli, suggesting the presence of apical K+ channels. 2. When Ringer solution was instilled, K+ was continuously removed from the alveoli and the K+ concentration in the instillate remained constant or decreased slightly depending on the rate of fluid absorption. The net K+ efflux from alveoli to blood was 0.23 pmol/(cm2 s). When Ba2+ was added to the instillate the net K+ efflux increased to 0.36 pmol/(cm2 s). Apical ouabain reversed the K+ flux resulting in a net K+ flux of 0.19 pmol/(cm2 s) into the alveoli. This suggests the presence of an Na+-K+-ATPase located in the apical membrane of some alveolar cells. 3. The K+ transport from instillate (Ringer solution) to perfusate was traced by means of 86Rb which was added to the instillate. Ouabain in the instillate did not affect fluid absorption but reduced the apparent 86Rb permeability by 50% although the paracellular permeability (estimated with [3H]mannitol) was unaffected. This also indicates the presence of an apical Na+-K+-ATPase. When ouabain was added to the perfusate, the apparent 86Rb permeability doubled. These findings indicate that recirculation of 86Rb (and K+) occurs due to the activity of both apical and basolateral Na+-K+-ATPases. 4. When ouabain was placed on both sides of the epithelium, preventing transcellular transport, the passive 86Rb permeability was 10.3 x 10(-8) cm/s (assuming an alveolar surface area of 5000 cm2). This value agrees with the passive permeabilities for mannitol, Na+ and Cl- suggesting that the paracellular pathway acts as a water-filled neutral channel. 5. We conclude that K+ is 'secreted' into the alveoli and is also removed from the alveoli, both processes being energized by Na+-K+-ATPases placed on the basolateral and apical sides, respectively. It is likely that two functionally different cell types exist in the alveolar membrane. One type ('B cell') has a Na+-K+-ATPase located at the basolateral membrane and K+ channels situated luminally.(ABSTRACT TRUNCATED AT 400 WORDS)

Absorption↗

PubMed1988

Maintained changes in motoneuronal excitability by short-lasting synaptic inputs in the decerebrate cat.

1. During investigation of the tonic stretch reflex in the unanaesthetized decerebrate cat we observed that a short train of impulses in Ia afferents from the soleus muscle (or its synergists) may cause a prolonged activity in the soleus muscle as judged by EMG and tension recordings. This excitability increase, which outlasted the stimulus train, could stay virtually constant during long periods (even minutes), but could be terminated at any time by a train of impulses in, for example, the peroneal nerve. 2. Gradation of the strength of stimulation and the duration of the train of impulses show that the amount of maintained excitability increase depends-within some limits-on the total amount of Ia impulses. 3. In paralysed preparations a short train of impulses in Ia afferents from any part of the triceps surae, caused a maintained increase of the efferent activity in the nerves to triceps surae and a maintained increase of the triceps surae monosynaptic test reflex. These experiments demonstrate the existence of a central mechanism (in the spinal cord and/or the brain stem), which is responsible for the maintained excitability increase seen in motoneurones to the homonymous and synergic muscles. 4. In acute spinal preparations it was not possible to demonstrate any long-lasting excitability increase by a train of Ia impulses. Following intravenous administration of the serotonin precursor 5-hydroxytryptophan, mimicking the tonic activity of these pathways in the decerebrate state, it was again possible to elicit the long-lasting excitability increase by a train of impulses in Ia afferents. A subsequent I.V. injection of methysergide (a serotonin receptor blocker) abolished the long-lasting excitability increase. This set of experiments demonstrates that the basic mechanism responsible for the maintained excitability increase is located at segmental level, and involves serotonergic systems. 5. It was demonstrated that activation of several ipsilateral and crossed reflex pathways by trains of impulses in cutaneous or high-threshold muscle afferents could trigger a maintained excitability increase of those motoneurone pools which were activated by the stimulation. Trains of stimuli to facilitatory regions in the brain stem could also cause a long-lasting excitability increase of motoneurones. Furthermore, activation of all reflex pathways which mediate postsynaptic inhibition to a motor nucleus (including recurrent inhibition via Renshaw cells) could terminate the prolonged excitability increase of that particular motor nucleus.(ABSTRACT TRUNCATED AT 400 WORDS)

5-Hydroxytryptophan↗

PubMed1988

Presynaptic inhibition of sympathetic fibers participating in vasodilatation in response to K+-induced contraction of frog skeletal muscle.

Experiments were performed on an autoperfused transparent frog muscle (m. cutaneus pectoris) with the purpose of elucidating possible mechanisms of functional hyperaemia. The diameter of a primary arteriole was followed before and after a K+-induced contracture lasting 20 s. The vasodilatation following this period of activity was expressed as the diameter change relative to the maximal possible diameter increase. The results emphasize adenosine as an important substance participating in vasodilatation in active skeletal muscle, its effect possibly being presynaptic (prejunctional) inhibition of sympathetic vasoconstrictor fibers to arteriolar smooth muscle (sympathetic uncoupling), in addition to the well-known direct effect (relaxation) on vascular smooth muscle cells. The presence of a strong resting sympathetic tone was demonstrated by local application of phentolamine (7.1 X 10(-5) M) that led to a large diameter increase. The purinoceptor blocking agent, 8-phenyltheophylline (8-PTP) invariably attenuated post-contraction vasodilatation, the adenosine transport inhibitor dipyridamole (10(-5) M) increased the hyperaemia response. Lack of sympathetic arteriolar tone during hyperaemia was demonstrated by the absence of a dilatory effect of phentolamine applied in the post-contraction period. Conversely, blockage of purinoceptors by 8-PTP during and after the contracture allowed sympathetic discharge to continue as verified by application of phentolamine, now leading to further vasodilatation. We suggest that presynaptic inhibition of sympathetic nerve endings by adenosine participates in vasodilatation in frog skeletal muscle.

Adenosine↗

PubMed1987

cAMP and beta-adrenergic stimulation of rat alveolar epithelium. Effects on fluid absorption and paracellular permeability.

The absorption of fluid (bicarbonate-buffered Ringer with 10 mmol/l glucose) instilled into rat lungs is a Na+-coupled process that takes place through two apical transport systems: an amiloride-sensitive Na+ transport and a Na+-glucose co-transport. Fluid absorption in isolated, perfused rat lungs and the permeability to 3H-mannitol of alveolar epithelium were studied in control conditions and during stimulation of the alveolar epithelium by cAMP or isoproterenol. cAMP led to a threefold increase in the rate of fluid absorption and to an increase in the paracellular permeability. A similar response was found following beta-adrenergic stimulation obtained with isoproterenol in the perfusate. The increase in fluid transport was due to enhancement of the amiloride-sensitive component of Na+ transport. The Na+-glucose co-transport which accounts for about 60% of fluid absorption in control conditions was depressed, possibly as a consequence of a depolarization of the apical alveolar cell membrane. Fluid absorption was reduced by 40% by apical amiloride (10(-4) mol/l) in control lungs and to an even larger extent in isoproterenol-stimulated lungs; it was completely abolished by amiloride in cAMP stimulated lungs. Since the Na+-glucose co-transport was still operative, this suggests that a secretory process was triggered. This was confirmed in experiments in which both kinds of transport were inhibited with a combination of amiloride and glucose-free Ringer. In these conditions fluid balance was zero in unstimulated lungs whilst fluid entry into alveoli was observed in isoproterenol and cAMP stimulated lungs.

Absorption↗

PubMed1987

Significance of active ion transport in transalveolar water absorption: a study on isolated rat lung.

1. Experiments were performed on isolated rat lungs perfused with Ringer solutions containing red cells. The goal was to clarify the role of active transport of Na+ for the absorption of fluid across the alveolar membrane, and to characterize active and passive pathways. 2. Partially degassed lungs were filled with 5 ml of an isotonic Ringer solution containing 125I-labelled albumin in order to calculate the fluid movement, and 22Na+ or 36Cl- for measurement of ion fluxes. Passive non-electrolyte permeability was determined in all experiments using [3H]mannitol. 3. The average rate of fluid absorption in phosphate-buffered instillates was 134 nl/s (S.E., 18.5; n = 14). With ouabain (10(-4) M) in the perfusate the fluid absorption rate fell to 57 nl/s (S.E., 8.2; n = 18). Amiloride (10(-3)-10(-4) M) in the instillate reduced the absorption to 75 nl/s (S.E., 8.6; n = 16). These results show that fluid absorption depends on transcellular transport of Na+ and that alveolar epithelial cells have a Na+ entry system in the luminal membrane and a Na+-K+ pump in the abluminal membrane. 4. The transcellular ion transport operates in parallel with a paracellular, passive leak that allows mannitol to pass with a permeability surface area product of 1.2 X 10(-4) ml/s, corresponding to a permeability coefficient of 2.4 X 10(-8) cm/s, assuming an alveolar surface area of 5000 cm2. 5. The passive fluxes of Na+ were 9.4 pmol/(cm2s) (S.E., 1.3; n = 25) in the direction from alveoli to perfusate and 8.0 pmol/(cm2s) (S.E., 0.86; n = 6) from perfusate to plasma. The passive fluxes of Cl- in the two directions were not significantly different either. Thus the transalveolar electrical potential difference is too small to affect ion movements measurably. 6. The passive permeability to Na+ was 6.7 X 10(-8) cm/s and to Cl- was 10.2 X 10(-8) cm/s (alveolar surface area assumed to be 5000 cm2). The ratio of the permeabilities is close to the ratio of the diffusion coefficients in free solution, suggesting a neutral or weakly charged paracellular channel. 7. We conclude that the alveolar epithelium performs solute-coupled fluid transport from alveoli to plasma, and that it shows many features that are common to other fluid-transporting epithelia; with an approximate surface area of 100 m2 in humans it constitutes one of the largest epithelial surfaces in the body.(ABSTRACT TRUNCATED AT 400 WORDS)

Absorption↗

PubMed1987

Fluid absorption by rat lung in situ: pathways for sodium entry in the luminal membrane of alveolar epithelium.

1. The purpose of the investigation was to characterize the luminal membrane and the paracellular pathway of rat lung alveolar epithelium. Experiments were performed on lungs in situ instilled with isotonic, buffered Ringer solution and perfused with blood from a donor rat using cross-circulation technique. 2. The rate of active Na+ transport was 4.4 pmol/(cm2s). The fluid absorption was 156 nl/s, and was unaffected by the presence of protein in the instillate (166 nl/s). In the absence of Na+, fluid absorption was zero. Amiloride (10(-3) M) reduced fluid absorption by 60%. Amiloride, combined with absence of D-glucose, arrested fluid absorption completely. Phloridzin at the luminal side reduced fluid absorption whilst phloretin had no effect. Amiloride together with phloridzin (10(-3) M) also arrested absorption. Thus, there are two entry systems for Na+ in the luminal membrane: Na+ channels and a Na+-D-glucose symport. These results show that alveolar fluid absorption is due to cellular activity. 3. Substitution of Cl- with gluconate not only stopped fluid absorption, but led to slight reversal of net fluid movement. 4. Passive unidirectional flux of Na+, determined with 22Na+, was 9.9 pmol/(cm2s) and that of Cl-, determined with 36Cl-, was 12.4 pmol/(cm2s). These fluxes were based on an assumed alveolar surface area of 5000 cm2. Transference numbers calculated from these figures are close to those in free solution, suggesting a neutral or weakly charged intercellular junctional pathway. The D-mannitol permeability in the paracellular pathway was 1.7 X 10(-8) cm/s. 5. It is a consequence of the proposed mechanism for fluid absorption that it becomes inoperative if the normally high reflexion coefficients for Na+ and Cl- are lowered in pathological states. In such conditions pulmonary oedema may develop depending on the net balance of passive mechanical and colloid-osmotic forces. 6. An explanation of the reversal of fluid transport at the time of birth is presented.

Absorption↗

PubMed1987

Reciprocal Ia inhibition between ankle flexors and extensors in man.

1. Reciprocal inhibition between antagonist muscle groups at the ankle has been investigated in sixty healthy subjects. Hoffmann reflexes (H reflexes) in the soleus and tibialis anterior muscles were used to assess changes in reciprocal inhibition evoked by electrical stimulation of antagonist muscle nerves. 2. Inhibition of the soleus H reflex was evoked by a single conditioning stimulus to the common peroneal nerve, and inhibition of the tibialis anterior H reflex was elicited by one conditioning stimulus to the posterior tibial nerve. Symmetrical central connections between the antagonist flexors and extensors were assumed and under this assumption the central delay for the inhibition, in addition to the delay for monosynaptic Ia excitation, was calculated to be about 1 ms. The inhibition was evoked by weak stimuli to the nerves from antagonist muscle groups; the threshold for the inhibition was around 0.6 X threshold for a direct motor response (M-threshold). Furthermore, tendon taps to the Achilles tendon facilitated the soleus H reflex and inhibited the tibialis anterior reflex at short latencies. The short central delay, the low electrical threshold and the.actions of Achilles tendon taps strongly suggest that the early reciprocal inhibition is homologous to the disynaptic Ia inhibition previously studied in animal experiments. 3. With the test soleus H reflex kept at 15-25% of the maximum directly evoked motor response (M-response) and the strength of the conditioning peroneal nerve stimulation kept at 1.0 X M-threshold, the inhibition from the peroneal nerve ranged between 0 and 40% (mean, 14.9%) at rest. 4. Changes in the amount of reciprocal inhibition from the peroneal nerve were studied both during tonic and dynamic dorsi- and plantarflexion. During tonic dorsiflexion there was no significant change of inhibition as compared to rest, while inhibition decreased during tonic plantarflexion. However, during ramp-and-hold dorsiflexion there was a transient increase in reciprocal inhibition of the soleus H reflex. This increase in inhibition from the peroneal nerve could be seen 50 ms prior to the onset of contraction. The increase in inhibition before and at the very beginning of the contraction cannot be due to sensory feed-back during contraction, but must depend on a supraspinal control of the spinal cord. 5. At conditioning-test intervals of 4-6 ms, the inhibition of the soleus H reflex from the peroneal nerve was considerably larger during tonic dorsiflexion than at rest. Thus, tonic dorsiflexion revealed an inhibition with long latency from the peroneal nerve, which was not seen at rest.(ABSTRACT TRUNCATED AT 400 WORDS)

Achilles Tendon↗

PubMed1987

The Malpighi lecture. From 'Porositates carnis' to cellular microcirculation.

After Malpighi's discovery of the capillaries almost 200 years elapsed before clear concepts about their main function, solute transport between blood and tissue, were formulated. The German physiologist Carl Ludwig played a significant role in this development because of his will to seek physico-chemical explanations of physiological phenomena. Ludwig's pupil Christian Bohr formulated the first (and almost definitive) mathematical model of transcapillary diffusion, later extended by Bohr's pupil August Krogh, to describe blood-tissue exchange in peripheral tissues. In the 1950s the two-pore model of transcapillary transport became the main paradigm (Pappenheimer, Grotte). The morphological substrate for this concept is found in tortuous pathways in the interendothelial junctions together with a small number of 'leaks' or focal openings in the capillary wall. The concept makes transcapillary transport of hydrophilic molecules a paracellular phenomenon. Recent studies in the author's laboratory based on electrophysiological methods on single capillaries have disclosed the rapidity of changes in microvascular permeability in response to many different substances--indicating reactions elicited in the endothelial cells. It is almost certain that in many cases, these changes are mediated via a transitory increase in cytosolic free calcium concentration. The overlap between permeability-increasing substances and agents that induce formation of endothelial-derived relaxing factor, EDRF, is so striking that a possible connection between vasodilatation and subtle increase in permeability should be considered. It is likely that the endothelial system of plasmalemmal invaginations ('vesicles') plays a role in the control of cytosolic calcium concentration.

Biological Transport↗

PubMed1986

Substances that rapidly augment ionic conductance of endothelium in cerebral venules.

Classical techniques for studying modulations of microvascular permeability have a time resolution of minutes. A newly developed method allows continuous measurement of the electrical resistance of the microvascular membrane in vivo (Olesen & Crone 1983). The technique exploits microelectrodes impaled into the vascular lumen and is based on cable analysis of the vessel. It was applied to venules on the surface of the frog brain to test the effect on microvascular permeability of a wide variety of substances. The following agents increased ionic permeability reversibly within seconds: 5-hydroxytryptamine, bradykinin, ATP, ADP, AMP, phospholipase A2, arachidonic acid, leukotriene C4, oxygen-derived free radicals, ionophore A23187, and unbound Evans blue dye. An irreversible permeability increase was induced by protamine sulphate, neuraminidase, trypsin, melittin, and snake venoms from Crotalus durissus terrificus and Bothrops atrox. The following substances were without effect within an administration period of 5 min: histamine, epinephrine, putrescine, angiotensin II, vasoactive intestinal polypeptide (VIP), substance P, neurotensin, vasopressin, adenosine, PGE2, PGF2 alpha, prostacyclin (PGI2), leukotriene B4, albumin, heparin, plant cytokinins, hyaluronidase, thrombin, wasp venom. Variations in pH between 5.1 and 8.6 did not change permeability. Three conclusions are drawn from the observations: (1) the permeability of cerebral microvessels can be modulated by specific agents, (2) the agents induced changes in the endothelium within a few seconds, and (3) the rapid permeability increase induced by inflammatory mediators was less than two-fold and reversible within minutes.

Animals↗