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R J Lang

Publications and source records attributed to R J Lang.

54 records · Page 3Linked to original sources

Mechanisms of action of noradrenaline and carbachol on smooth muscle of guinea-pig anterior mesenteric artery.

Membrane potential was recorded by micro-electrode in segments of small (200-500 microns o.d.) mesenteric arteries of guinea-pig. Isotonic shortening was recorded in helical strips cut from these arteries. Raising the external potassium concentration, [K+]o, caused shortening and substantial depolarization. The threshold for contraction was about 30 mM which corresponded to a membrane potential of about -45 mV. Since high-potassium contractions were abolished in calcium-free solution it was suggested that they occur due to potential-sensitive calcium channels opening positive to about -45 mV. Noradrenaline weakly depolarized the muscle and produced contractions resistant to calcium-free conditions. It was suggested that noradrenaline contractions are mainly caused by mechanisms other than the opening of potential-sensitive calcium channels, namely entry of calcium via other channels and release of stored calcium. Carbachol had no effect on basal tension but inhibited shortening by noradrenaline or by raising [K+]o. The inhibitory effect of carbachol on tension under various conditions was associated with hyperpolarization or depolarization in a range negative to -45 mV, or no effect on potential, so that modulation of the number of open potential-sensitive calcium channels could not be evoked to explain its relaxant action. Removal or destruction of the endothelium by rubbing or by distilled water perfusion left tension responses to noradrenaline or raised [K+]o essentially unchanged. However, the inhibitory effect of carbachol on tension was attenuated and hyperpolarization of the resting artery was converted to a depolarization. It was concluded that carbachol has both a strong inhibitory and a weak excitatory effect on these vascular smooth muscle cells. Membrane potential changes are not essential to its inhibitory action but may, by closing potential-sensitive calcium channels, sometimes reinforce it. Hyperpolarization by carbachol may be caused by a factor released by the action of carbachol on endothelial cells: in its absence carbachol may weakly depolarize but this alone is normally insufficient to generate tension.

Action Potentials↗

Maintenance of sterility in urinary drainage bags.

When the outlet tube of urinary drainage sets was kept full of 3 per cent hydrogen peroxide at all times, no evidence of bacterial growth in the urine of the collection bag was noted in at least 92.0 per cent of the patients and 93.3 per cent of the drainage periods in a group of 60 patients and 75 drainage periods. One patient had a positive urinary drainage bag culture and a positive bladder culture as a result of improper disconnection of the catheter, and four patients had bacterial growth from urinary drainage bag samples, two of which were possibly due to a faulty culture technique and one of which may have resulted from contamination of amphoteracin B irrigating solution. Hydrogen peroxide, 3 per cent, appears to approach 100 per cent effectiveness as an antibacterial barrier. Only one patient of 60 or 1.7 per cent had a urinary tract infection develop which was related to the improper handling of the drainage set.

Anti-Infective Agents↗

Mechanism of action of vasoactive intestinal polypeptide on myometrial smooth muscle of rabbit and guinea-pig.

1. The action of vasoactive intestinal peptide (VIP) on the electrical and mechanical activity of strips of longitudinal myometrial smooth muscle from rabbits and guinea-pigs treated with oestradiol was studied in the sucrose-gap apparatus. 2. In myometrial strips which spontaneously exhibited regular contractions, or which were induced to contract rhythmically to the application of oxytocin, VIP reduced both the frequency and the force of contraction. 3. Contractions were associated with bursts of action potential discharge. In guinea-pig, the membrane potential reached its most negative value shortly following a burst and a slow decay of negativity followed ("generator potential'). VIP inhibited the decay of this negativity and increased the duration of the period between bursts. In rabbit myometrical strips, electrical discharges occurred less regularly but VIP also had an inhibitory action. The inhibitory action of VIP was not affected by the beta-adrenoreceptor blocker propranolol, by tetrodotoxin, or by apamin. 4. Using the double sucrose-gap apparatus, bursts of action potentials and contractions were elicited with depolarizing electrical pulses in the absence of oxytocin. Changes in membrane resistance were also estimated by eliciting hyperpolarizing electrotronic potentials. VIP hyperpolarized the membrane and inhibited contractions as depolarizing pulses now failed to reach threshold for action potential discharge or fewer action potentials were discharged. A small (about 10%) reduction in membrane resistance was freqeuently observed during the hyperpolarization. 5. If a single action potential was elicited in the presence of VIP, the tension generated by the muscle was less than in its absence. 6. In a calcium-free high-potassium (126 mM) solution, readmitting calcium produced contraction; VIP inhibited this contraction. Activation of beta-receptors by means of isoprenaline had a similar effect but unlike isoprenaline the action of VIP was not blocked by propranolol. 7. It is suggested that the primary action of VIP is on the calcium economy of the myometrial smooth muscle cell, possibly to accelerate sequestration and/or extrusion of calcium from the cell. In some way this is associated with inhibition of the generator potential, hyperpolarization, and with a small increase in permeability of the membrane to potassium.

Action Potentials↗

Evidence that histamine and carbachol may open the same ion channels in longitudinal smooth muscle of guinea-pig ileum.

1. Membrane potential was recorded intracellularly by micro-electrode in separated longitudinal muscle of guinea-pig ileum. Electrotonic potentials were evoked in longitudinal strips by passing current between large external electrodes in the partition chamber.2. Histamine increased the frequency of action potential discharge at low concentrations and depolarized the membrane. At higher concentrations it caused substantial depolarization and action potential discharge was abolished. Carbachol had similar actions but the maximal depolarization by carbachol (using 10(-4)m) was some 4-5 mV greater than maximal depolarization by histamine (using 10(-4)m).3. The change in size of evoked electrotonic potentials was used to estimate the effects of carbachol and histamine on the conductance of the smooth muscle membrane. The equilibrium potentials for histamine and carbachol depolarizations were estimated from their relative effects on potential and conductance and were found to be not significantly different; measurements of the effects on conductance showed that 10(-4)m-histamine increased conductance about 8-fold whilst 10(-4)m-carbachol had a much greater effect on conductance. This difference could explain the differing maximal depolarizing effects of these agents if both were assumed to open channels having the same ionic selectivity (i.e. equilibrium potential).4. The efflux of (42)K was studied in separated strips of longitudinal ileal muscle from guinea-pig. In the presence of a concentration of carbachol (2 x 10(-5)m or 10(-4)m) having a maximal effect on (42)K efflux rate, histamine (10(-4)m) did not increase efflux further although 120 mm-potassium did so. Experiments with the irreversible muscarinic receptor blocker, propylbenzilylcholine mustard, indicated that the number of muscarinic receptors did not limit the (42)K efflux response to carbachol and it was suggested that the response was limited by the availability of ion channels which could be opened by activated muscarinic receptors.5. Contractions to histamine and carbachol in 120 mm-potassium depolarizing solution were followed upon washing by a relaxation below basal tension. Carbachol, but not histamine, showed a pronounced and long lasting secondary contraction following this relaxation.6. These results are consistent with the idea that activated histamine and activated muscarinic receptors open the same ion channels in the smooth muscle membrane to produce depolarization, increased action potential discharge and contraction, although muscarinic receptors can open more of these. However, there was evidence that the opening of these channels is not the only pathway between receptor activation and contraction.

Animals↗

Temperature and inhibitory junctional transmission in guinea-pig ileum.

The effects of temperature on the inhibitory junctional potential (i.j.p.) and the electrotonic potential, recorded in the circular smooth muscle of the guinea-pig ileum, were studied with intracellular microelectrodes. The amplitude and time course of the i.j.p. were both dependent on the ambient temperature, the i.j.p. becoming smaller and more prolonged as the temperature was lowered. In contrast, the electrotonic potential was not much affected by temperature. The atropine-resistant 'late' depolarization was also dependent on temperature. These results are consistent with the mechanism of release, of the nonadrenergic noncholinergic inhibitory transmitter, being sensitive to temperature and with the inhibitory conductance change, underlying the i.j.p., being long compared to the membrane time constant of the circular smooth muscle.

Animals↗

The effects of calcium and magnesium ions, temperature and repetitive stimulation on inhibitory junctional transmission in smooth muscle of guinea-pig small intestine.

1 The effects of calcium and magnesium ions and temperature on the peak amplitude of the nonadrenergic, noncholinergic inhibitory junction potential, evoked by a single stimulus, or paired transmural stimuli, were examined in the circular muscle of guinea-pig small intestine.2 The peak amplitude of the inhibitory junction potential (i.j.p.) could be decreased by lowering the external concentration of calcium or by raising the external magnesium concentration (at 25 degrees C).3 At 25 degrees C, the second of a pair of i.j.ps was larger than the first at short intervals (<0.2 s), but smaller at larger intervals (0.2 to 20 s). Enhancement of the second (test) response decayed exponentially with a time constant of 87 ms. Depression of the test i.j.p. was maximal at 0.4 s and then recovered exponentially with a time constant of 11 s.4 In low calcium or high magnesium solution, depression of the test i.j.p. decreased without any change in the rate of recovery from depression.5 Despite the slow rate of recovery from depression after a single conditioning response, transmitter output could be maintained during low-frequency repetitive stimulation.6 The peak amplitude of the i.j.p. increased as the temperature was raised to 35 degrees C (Q(10) = 1.5).7 In contrast to the neuromuscular junction, the depression of the second of a pair of i.j.ps decreased as the temperature was raised. At 35 degrees C the test i.j.p. was larger than the conditioning i.j.p. for most stimulus intervals (1 to 20 s).8 The results suggest that the rate of replenishment of the store of inhibitory transmitter is sensitive to both temperature and repetitive stimulation.

Animals↗

Dimensionality of the perceived self: the Tennessee Self Concept Scale.

The 12 indices of self-perception in the Tennessee Self Concept Scale, together with the Eysenck Personality Inventory, were factor analysed using data obtained from psychiatric day-care patients (n = 131). Separate item- and scale-level factor analyses revealed that: (1) the five external and three internal domains of self-concept, hypothesized as distinct, may be accurately viewed as lying in one-dimensional space; (2) the conflict, variability and distribution scores are unrelated to subtype of self-esteem; (3) extraversion and neuroticism form a bipolar factor that is orthogonal to self-concept; and (4) the emergence of 30 item-factors with a 30 per cent factorial overlap implies a good deal of spuriously shared variance, low inter-scale homogeneity and sizable redundancy in the TSCS scales. Owing to these results, the construct and factorial validity of the TSCS is seriously questioned. It is suggested that future researchers develop more sensitive, treatment-oriented (or idiographic) measures to compare man's less conspicuous and more private 'self-image feelings and cognitions' against his public self-disclosure in the interests of facilitating more rapid behavioural change.

Adolescent↗

Acetylcholine activates an inward current in single mammalian smooth muscle cells.

Acetylcholine, the major excitatory neurotransmitter to the smooth muscle of mammalian intestine, is known to depolarize smooth muscle cells with an apparent increase in membrane conductance. However, the ionic mechanisms that are triggered by muscarinic receptor activation and underlie this response are poorly understood, due in part to the technical problems associated with the electrophysiological study of smooth muscle. The muscarinic action of acetylcholine in certain neurones has been shown to involve the switching off of a resting K+ current (M-current) and a similar mechanism has recently also been identified in smooth muscle of amphibian stomach. We have now applied the patch-clamp technique to single smooth muscle cells of rabbit jejunum and find that muscarinic receptor activation switches on a nonselective, voltage-sensitive inward current. In addition, acetylcholine activates and then suppresses spontaneous K+ current transients, which are probably triggered by rises in intracellular Ca2+ in these cells.

Acetylcholine↗

Interstitial cell of Cajal-like cells in the upper urinary tract.

Autorhythmicity in the upper urinary tract (UUT) has long been considered to arise in specialized atypical smooth muscle cells (SMC) predominately situated in the most proximal regions of the pyeloureteric system. These atypical SMC pacemakers have been thought to trigger adjacent electrically-quiescent typical SMC to fire action potentials which allow an influx of Ca2+ and the generation of muscle contraction. More recently, the presence of cells with many of the morphological, electrical and immunohistochemical characteristics of interstitial cells of Cajal (ICC), the pacemaker cells of the gastrointestinal tract, have been located in many regions of both the upper and lower urinary tract. This article reviews the evidence from the literature and from our laboratory supporting a role of both atypical SMC and ICC-like cells in the initiation and propagation of pyeloureteric peristalsis in the UUT. We propose a new model in which there are 2 populations of pacemaker cells, high frequency atypical SMC and lower frequency ICC-like cells, both of which can drive electrically-quiescent typical SMC. The relative presence of these 2 populations of pacemaker cells and the relatively-long refractoriness of typical SMC determines the decreasing frequency of contraction with distance from the renal fornix. In the absence of the proximal pacemaker drive from atypical SMC after pyeloureteral/ureteral obstruction or surgery, ICC-like cell pacemaking provides a compensatory mechanism allowing the ureter to maintain rudimentary peristaltic waves and movement of urine from the pyelon towards the bladder.

Animals↗

Influence of internal calcium stores on calcium-activated membrane currents in smooth muscle.

Agonist-induced activation of second messenger systems that increase inositol 1,4,5-trisphosphate concentration plays an important role in the mobilisation of stored Ca2+ in smooth muscle. Release of Ca2+ which occurs spontaneously or by agonist stimulation causes activation of Ca(2+)-sensitive currents. Experiments using selective modulators of the Ca2+ uptake and release mechanisms of the sarcoplasmic reticulum provide evidence that depletion of the internal Ca2+ store triggers an influx of Ca2+ from the extracellular space. Recent data suggest that pool depletion causes the opening of non-selective cation channels which are possibly similar to those previously designated 'receptor-operated Ca2+ channels'. Ca2+ entry through these channels not only refills the internal Ca2+ pool, but also modulates membrane excitability by stimulating Ca(2+)-activated currents.

Animals↗