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Biomedical subjects

J R Slack

Publications and source records attributed to J R Slack.

At least 19 recordsLinked to original sources
PubMed2002

Anisotropic propagation in the small intestine.

Abstract Measuring propagation anisotropy may help in determining the tissue layers involved in the propagation of electrical impulses in the intestine. We used 240 extracellular electrograms recorded from the isolated feline duodenum. The conduction velocities of slow waves and of individual spikes were measured from their site of origin into all directions. Both slow waves and spikes propagate anisotropically in the small intestine but in different directions and to a different degree. Slow waves propagated anisotropically faster in the circumferential (1.7 +/- 0.8 cm s(-1)) than in the axial direction (1.3 +/- 0.5 cm s(-1); P < 0.001). Spikes, on the other hand, propagated faster in the longitudinal direction (7.8 +/- 4.5 cm s(-1)) than in the circumferential direction (3.3 +/- 4.3 cm s(-1); P < 0.001). Furthermore, the average conduction velocity of spikes (6.3 +/- 4.5 cm s(-1)) was significantly higher than that of slow waves (1.5 +/- 1.1 cm s(-1); P < 0.001). The anisotropic propagation of spikes supports the argument that these propagate in the longitudinal muscle layer. The anisotropic propagation of slow waves may be the result of the interaction between the myenteric layer of interstitial cells of Cajal and their electrotonic connection to both the longitudinal and the circular muscle layer.

Action Potentials↗
PubMed2001

A role for protein kinase intracellular messengers in substance P- and nociceptor afferent-mediated excitation and expression of the transcription factor Fos in rat dorsal horn neurons in vitro.

Expression of the inducible transcription factor Fos in the spinal dorsal horn in vivo is associated with nociceptive afferent activation, but the underlying stimulation-transcription pathway is less clear. This in vitro spinal cord study concerns the role of protein kinase A and C second messengers in substance P receptor (NK1R)-mediated or nociceptive afferent-evoked neuronal excitation and Fos expression. Nociceptive afferent (dorsal root) stimulation of isolated spinal cords (10-14 day old rats) evoked a 'prolonged' excitatory polysynaptic potential (DR-EPSP) that was attenuated (P < 0.05) by: the protein kinase A inhibitor, Rp-cAMP; the protein kinase C inhibitor, bisindolymaleimide I; and the selective NK1R antagonist, GR82334. Neuronal excitations induced by the NK1R agonist [Sar9,Met(O2)11]-SP were attenuated by Rp-cAMP, bisindolymaleimide I and GR82334. Effects of the protein kinase A and C inhibitors on the DR-EPSP or the [Sar9,Met(O2)11]-SP-induced depolarization were nonadditive, suggesting convergence of these intracellular signalling pathways onto a common final target. Nociceptor afferent-induced Fos, detected by immunohistochemistry in superficial and deep dorsal horn laminae, was attenuated by Rp-cAMP, bisindolymaleimide I and GR82334. In spinal cords pretreated with TTX to eliminate indirect neuronal activation, [Sar9,Met(O2)11]-SP (1-20 microM) elicited a dose-related expression of Fos that was reduced by Rp-cAMP, bisindolymaleimide I and GR82334. The effects of these inhibitors were most pronounced in the deep laminae. These data support a causal relationship between protein kinase A- or C-dependent signal transduction, nociceptive afferent- or NK1R-induced neuronal excitation and Fos expression in dorsal horn. Implications for short- versus long-term modulation of nociceptive circuitry are discussed.

Animals↗
PubMed2001

Two-dimensional high-resolution motility mapping in the isolated feline duodenum: methodology and initial results.

Several types of electrical events occur in the small intestine but their spatial and temporal contributions to overall motility are not clear. In order to quantify local motility in greater detail, a new technique of recording and analysing movements at multiple sites was developed. Use was made of isolated segments of feline duodenum superfused in a tissue bath. Multiple marker dots (20-75) were placed on the serosal surface by applying fine spots of candle soot in rectangular arrays (1-2 mm dot separation). A digital video camera was used to record spontaneous movements of the dots for periods of 10-30 min. After each experiment, 4-6 periods (10-60 s each) of video frames were transferred to a computer (25 fps, 720 x 576 pixels) and the movements of the dots was tracked every 40 ms using custom-made software. Initial results (eight experiments) show that spontaneous motility is remarkably variable, both in space and time. Three types of movement could be discerned: (i) periodic, rolling or pendular movements, with a frequency of approximately 15 min-1 occurring predominantly in the longitudinal direction; (ii) twitches, wherein a subset of dots were suddenly displaced longitudinally; and (iii) drifts of most of the dots in a circular or oblique direction. All three types of movement occurred throughout every recording session although their relative magnitudes differed greatly from moment to moment. Occasionally, it was possible to detect propagated 'contractions' with an apparent velocity of 10 mm s(-1). Immobilizing the preparation at one point by inserting a needle through the middle of the array of markers had a negligible effect on the displacements, whereas application of verapamil (10(-5) mol L(-1)) reduced or abolished motility. In summary, we present a new technique to map in detail two-dimensional motility at the surface of the intestine. Initial results seem to suggest that motility at the serosal surface is not uniform and highly anisotropic.

Animals↗
PubMed2001

Of slow waves and spike patches.

In the small intestines, the major task of the slow wave is to induce mechanical movements in the intestinal wall by generating local calcium spikes. High resolution electrical mapping reveals fundamental differences in propagation between slow waves and calcium spikes. These differences suggest that slow waves and spikes are propagated by different mechanisms through different cell networks.

Action Potentials↗
PubMed2000

The spatial behaviour of spike patches in the feline gastroduodenal junction in vitro.

In the isolated feline gastroduodenal region, the spatial propagation of slow waves and of individual spikes was reconstructed. Recordings were performed simultaneously from 240 extracellular electrodes positioned on the serosal surface across the junction. Results from nine experiments (22 slow waves) showed that the slow wave never propagated across the gastroduodenal region and that this block was due to the presence of a zone of quiescence caudal to the pylorus. In contrast, spikes (n=155) were able to propagate into the quiescent zone, either from the antrum (15.4%) or from the duodenum (34.0%) and occasionally, were able to propagate from one organ to the other (10.9%). However, in all cases, spike conduction was self-limited and activated a local area termed a 'patch'. The length of the patches located in the gastroduodenal region was significantly longer than in the rest of the duodenum (20.2 mm +/- 9. 7 vs. 9.5 mm +/- 3.2; P < 0.001) indicating a possible enhancement of spike propagation in this region. In conclusion, in spite of the total conduction block for slow waves, individual spikes are able to propagate across the gastroduodenal region, albeit in self-limited areas or 'patches'. These spike patches could form the building blocks for gastroduodenal coordination.

Action Potentials↗
PubMed1998

Role of extracellular [Ca2+] in fatigue of isolated mammalian skeletal muscle.

The possible role of altered extracellular Ca2+ concentration ([Ca2+]o) in skeletal muscle fatigue was tested on isolated slow-twitch soleus and fast-twitch extensor digitorum longus muscles of the mouse. The following findings were made. 1) A change from the control solution (1.3 mM [Ca2+]o) to 10 mM [Ca2+]o, or to nominally Ca2+-free solutions, had little effect on tetanic force in nonfatigued muscle. 2) Almost complete restoration of tetanic force was induced by 10 mM [Ca2+]o in severely K+-depressed muscle (extracellular K+ concentration of 10-12 mM). This effect was attributed to a 5-mV reversal of the K+-induced depolarization and subsequent restoration of ability to generate action potentials (inferred by using the twitch force-stimulation strength relationship). 3) Tetanic force depressed by lowered extracellular Na+ concentration (40 mM) was further reduced with 10 mM [Ca2+]o. 4) Tetanic force loss at elevated extracellular K+ concentration (8 mM) and lowered extracellular Na+ concentration (100 mM) was partially reversed with 10 mM [Ca2+]o or markedly exacerbated with low [Ca2+]o. 5) Fatigue induced by using repeated tetani in soleus was attenuated at 10 mM [Ca2+]o (due to increased resting and evoked forces) and exacerbated at low [Ca2+]o. These combined results suggest, first, that raised [Ca2+]o protects against fatigue rather than inducing it and, second, that a considerable depletion of [Ca2+]o in the transverse tubules may contribute to fatigue.

Action Potentials↗
PubMed1997

Profile of neuronal excitation following selective activation of the neurokinin-1 receptor in rat deep dorsal horn in vitro.

The excitatory actions of the selective neurokinin-1 receptor (NK1R) agonist [Sar9,Met(O2)11]substance P (SP) were tested on a sample (n = 50) of deep dorsal horn neurones in the isolated and hemisected young rat spinal cord. Superfusion of the NK1R agonist (2 microM) elicited a prolonged membrane depolarisation (6.6 +/- 0.5 mV) and an increase in action potential firing in 41/50 (82%) neurones. These [Sar9,Met(O2)11]SP-induced depolarisations were attenuated by the selective NK1R antagonist GR82334 (1 microM). An increased neuronal excitability after [Sar9,Met(O2)11]SP application was indicated by an augmented spike frequency generated in response to long duration, step depolarisations. In order to assess whether a direct excitatory action existed, [Sar9,Met(O2)11]SP was re-tested on a sample of TTX-treated neurones (n = 14). The majority (9/14) retained agonist sensitivity although the amplitude of the depolarisation was reduced to 48% of the control value. A sample of neurones (n = 7) that responded to the NK1R agonist were morphologically characterised after filling with the intracellular dye, biocytin. Dorsal dendrites that clearly penetrated lamina II and that could receive a direct C-afferent input, were identified in only 2/7 neurones. These electrophysiological and neuroanatomical data demonstrate that deep dorsal horn neurones possess functional NK1Rs. The implications of the existence of these NK1Rs in the context of spinal somatosensory systems and SP is considered.

Animals↗
PubMed1997

Tachykinin actions on deep dorsal horn neurons in vitro: an electrophysiological and morphological study in the immature rat.

To assess whether functional neurokinin receptors exist in the deep dorsal horn of the rat, the actions of the selective neurokinin-1 receptor (NK1R) agonist [Sar9,Met(O2)11]substance P ([Sar9,Met(O2)11]SP), the neurokinin-2 receptor (NK2R) agonists [beta-Ala8]NKA(4-10) and GR64349 and the neurokinin-3 receptor (NK3R) agonist senktide were examined intracellularly in vitro. [Sar9,Met(O2)11]SP (1-4 microM) and senktide (1-2 microM) elicited slow depolarizations (<10 mV) associated with increased synaptic activity and cell firing. [beta-Ala8]NKA(4-10) (10-20 microM) and GR64349 (0.25-10 microM) caused small depolarizations (<2.0 mV) and no firing. Neurons were categorized as either 'tonic' or 'phasic' depending on their firing response to direct current step depolarizations. Tonic neurons, which, unlike phasic neurons, display no spike firing accommodation, generated a significantly larger depolarization to the NK1R and NK3R agonists. The putative contribution of these receptors to primary afferent-mediated synaptic transmission was assessed by testing the NK1R antagonist GR82334 (1 microM), the NK2R antagonist MEN10,376 (1 microM) and the NK3R antagonist [Trp7,beta-Ala8]NKA(4-10) (1 microM) against the dorsal root-evoked excitatory postsynaptic potential (DR-EPSP). GR82334 and [Trp7,beta-Ala8]NKA(4-10) significantly reduced (P < or = 0.05) the duration but not the amplitude of the DR-EPSP. MEN10,376 (1 microM) had no effect on DR-EPSP amplitude or duration. Morphological detail was obtained for seven biocytin-filled deep dorsal horn neurons tested with [Sar9,Met(O2)11]SP. Five neurons responded to the NK1R agonist, and two of these had dorsally directed dendrites into the substantia gelatinosa. The other three [Sar9,Met(O2)11]SP-sensitive neurons had dendrites within deeper laminae. These data support the existence of functional NK1Rs and NK3Rs in the deep dorsal horn which may be involved in mediating sensory afferent inputs from nociceptors.

Animals↗
PubMed1997

Different effects of raised [K+]o on membrane potential and contraction in mouse fast- and slow-twitch muscle.

Increasing extracellular K+ concentration ([K+]o) from 4 to 7-14 mM reduced both tetanic force and resting membrane potential (Em) in isolated slow-twitch soleus and fast-twitch extensor digitorum longus (EDL) muscles of the mouse. The tetanic force-[K+]o relationships showed a greater force loss over 8-11 mM [K+]o in soleus than EDL, mainly because the Em was 2-3 mV less negative at each [K+]o in soleus. The tetanic force-resting Em relationships show that force was reduced in two phases: phase 1 (Em < -60 mV), a 20% force decline in which the relationships superimposed in soleus and EDL, and phase 2 (Em -60 to -55 mV), a marked force decline that was steeper in EDL than soleus. Additionally in phase 2, longer stimulation pulses restored tetanic force; the twitch force-stimulation strength relationship was shifted toward higher voltages; caffeine, a myoplasmic Ca2+ concentration elevator, increased maximum force; and twitch force fell abruptly. We suggest that 1) the K(+)-depressed force is due to reduced Ca2+ release resulting from an altered action potential profile (phase 1) and inexcitable fibers due to an increased action potential threshold (phase 2), and 2) K+ contributes to fatigue in both fast- and slow-twitch muscle when it causes depolarization to about -60 mV.

Animals↗
PubMed1995

Effects of a cAMP analogue simulate the distinct components of long-term potentiation in CA1 region of rat hippocampus.

Bath application of the cAMP analogue, dibutyryl cyclic adenosine 3',5'-monophosphate (dibutyryl cyclic AMP; dbcAMP) to rat hippocampal slices was found to potentiate both the CA1 population spike and population excitatory post-synaptic potential (EPSP) slope. dbcAMP (500-1000 microM) was applied to slices for 30 min; following washout the population EPSP slope was potentiated for at least 30 min to a mean value of 51% above the drug-free baseline value. The population spike was similarly potentiated to a mean value of 64% above baseline after dbcAMP washout. dbcAMP-induced population EPSP slope potentiation occluded long-term potentiation (LTP) induced by high frequency electrical stimulation, and LTP occluded dbcAMP-induced EPSP slope potentiation. Earlier investigations (Pockett et al., Neuroscience, 52 (1993) 229-236) using 200 microM dbcAMP reported similar potentiation of population spike but no potentiation of EPSP slope. These experiments support the hypothesis that the two components of LTP (Bliss and Lynch, In P.W. Landfield and S.A. Deadwyler (Eds.), Long-term Potentiation: from Biophysics to Behaviour, Alan R. Liss, New York, 1988, pp. 3-72) in the CA1 area of rat hippocampus both involve distinct cAMP-dependent mechanisms.

Animals↗
PubMed1995

Sacroiliac joint manipulation decreases the H-reflex.

Joint manipulation is widely utilized clinically to decrease pain and increase the range of motion of joints displaying limited mobility. Evidence of efficacy is based on subjective reports of symptom improvement as well as on the results of clinical trials. Experiments were designed to determine whether or not sacroiliac joint manipulation affects the amplitude of the Hoffman (H) reflex. Surface EMG recordings of the reflex response to electrical stimulation of the tibial nerve in the popliteal fossa were made from the soleus muscle. The averaged amplitudes of H-reflexes were compared on both legs before and after either sacroiliac joint manipulation or a sham procedure. H-reflex amplitude was significantly decreased (12.9%) in the ipsilateral leg (p < 0.001) following a sacroiliac joint manipulation while there was no significant alteration following the sham intervention. There was no significant alteration in reflex excitability in the contralateral leg to the sacroiliac joint manipulation. To further investigate the mechanism of these reflex alterations, the local anaesthetic cream EMLA (Astra Pharmaceuticals) was applied to the skin overlying the sacroiliac joint and the experiments were repeated on a different group of subjects. This was intended to determine if excitation of cutaneous afferents was responsible for the reflex excitability changes. There was still a significant decrease in reflex excitability (10.6%) following sacroiliac joint manipulation (p < 0.001). These findings indicate that joint manipulation exerts physiological effects on the central nervous system, probably at the segmental level. The fact that the changes persisted in the presence of cutaneous anaesthesia suggests that the reflex changes are likely to be mediated by joint and/or muscle afferents.

Adolescent↗
PubMed1993

Cyclic AMP and long-term potentiation in the CA1 region of rat hippocampus.

Bath application of dibutyryl cyclic AMP, 8-bromo cyclic AMP or forskolin to hippocampal slices caused a short-lasting decrease, followed after washout by a long-lasting increase in the amplitude of population spikes recorded in area CA1 in response to 0.05 Hz stimulation of the Schaffer collateral/commissural pathway. Population spike depression lasted only as long as the cyclic AMP analogues were present in the bath, while the potentiation lasted for at least 2 h after they were washed out. Population excitatory postsynaptic potential amplitude was depressed while dibutyryl cyclic AMP was present in the bath, but after washout it was not significantly different from baseline amplitude. The population spike depression caused by dibutyryl cyclic AMP was prevented by the adenosine antagonist 8-p-sulfophenyltheophylline, but the long-lasting potentiation was not. Thus the transient depression induced by dibutyryl cyclic AMP was probably caused by an action of the drug or its breakdown products as adenosine agonists. The long-lasting potentiation is caused by a different mechanism. Occlusion experiments were performed to examine the relationship of the long-lasting population spike potentiation caused by dibutyryl cyclic AMP to the population spike long-term potentiation caused by high-frequency stimulation. High-frequency stimulation delivered after the population spike potentiation caused by dibutyryl cyclic AMP was established did cause a further potentiation, but only up to the level caused by high-frequency stimulation alone. Dibutyryl cyclic AMP administered after high frequency stimulation-induced long-term potentiation was established had no further potentiating effect.(ABSTRACT TRUNCATED AT 250 WORDS)

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1991

Cyclic AMP induces long-term increase in synaptic efficacy in CA1 region of rat hippocampus.

The membrane permeable cyclic AMP analogue dibutyryl cAMP was found to have a biphasic effect on the amplitude of population spikes recorded in area CA1 of rat hippocampal slices in response to 0.05 Hz stimulation of the Schaffer collateral/commissural path. While dbcAMP was present the population spike was depressed and after washout of dbcAMP the population spike showed potentiation lasting at least 2 h. The population excitatory postsynaptic potential (EPSP) was unaffected. Addition of picrotoxin throughout the experiment caused no change in the depression but reduced the potentiation caused by dbcAMP. We conclude that cAMP may play a role in long-term potentiation (LTP).

Animals↗
PubMed1991

Presynaptic activity in the period immediately after conditioning is not necessary for long-term potentiation.

The stratum radiatum of in vitro slices of rat hippocampus was tetanically stimulated to induce long-term potentiation (LTP) in CA1 neurons. One group of slices received test stimuli immediately after tetanisation, whilst another received no test stimuli until 30 min afterwards. No difference (P greater than 0.65) was found between the magnitude of LTP induced in the two groups of slices. This result demonstrates that the induction and maintenance of LTP does not require presynaptic release of transmitter or other neuroactive substances in the period immediately after tetanisation.

Animals↗
PubMed1989

Competition for survival between motor units in mouse skeletal muscle.

The soleus nerve on one side of neonatal mice was crushed and the soleus muscle on the same side was surgically reduced in size. Some animals also had their lumbar spinal nerve 5 (L5) cut and misdirected in the same operation. Three months later, the number of L5 and L6 soleus motor units in the operated muscles was counted electrophysiologically and the number of muscle fibers was counted histologically. The number of L6 motor units in reduced size muscles without L5 innervation was significantly greater than it was in muscles where both L5 and L6 motor units were present. This result supports the concept that motor neuron survival during development is dependent upon the number of muscle fibers available for innervation and the number of motor neurons competing to innervate them.

Action Potentials↗
PubMed1984

Effect of nerve growth factor on intramuscular axons of neonatal mice.

Newborn mice were given daily injections of nerve growth factor over the gluteus muscle. At age 9 days muscles were removed and stained to reveal intramuscular axons. Motor axons, and sensory axons of the Golgi tendon organs and muscle spindles were unaffected by nerve growth factor, but there was prolific growth of the small diameter axons that ramify over the surface of the muscle. These axons were sensory rather than sympathetic, since the degenerated following dorsal root ganglionectomy but not following sympathetic ganglionectomy. This finding supports the concept that nerve growth factor is involved in the development of sensory innervation of muscle.

Animals↗
PubMed1984

Muscle size and motor unit survival in mice.

The soleus muscles in neonatal and adult mice were surgically reduced in size on one side of the animal. The experimental and control muscles were excised 6-48 weeks later and the number of motor units in each muscle was estimated by stimulating the muscle nerve and counting step increments in the electromyogram recorded in vitro. Multiple innervation in individual muscle fibres was then assessed by intracellular recording and by visualization of end-plates in the light microscope with cholinesterase stain. Muscle fibres were counted in cross-sections of each muscle in the light microscope. Surgical reductions in the size of the muscle during the first 3 weeks of life produced correlated reductions in the number of motor units in the muscle. This could not be attributed to masking of motor units by multiple innervation, which was always less than 10% in these muscles. The loss of motor units was greatest following reduction in muscle size in newborn mice, whereas in 6-week-old mice there was no significant loss of motor units following the operation. Thus, survival of neonatal motor units shows an age-related dependence on the number of muscle fibres available for innervation. In control muscles there was a highly significant correlation between motor unit and muscle fibre numbers, which is consistent with the hypothesis that motor neurone survival during the embryonic period of cell death is dependent upon the number of muscle fibres available for innervation.

Age Factors↗