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Biomedical subjects

J S Kelly

Publications and source records attributed to J S Kelly.

At least 163 records · Page 9Linked to original sources
PubMed1973

On the pharmacology of the gamma-aminobutyric acid receptors on the cuneo-thalamic relay cells of the cat.

1. gamma-Aminobutyric acid (GABA) and glycine applied by iontophoresis were equipotent depressants of cuneo-thalamic relay neurones isolated from the middle third of the cuneate nucleus of cats either decerebrated or anaesthetized with sodium pentobarbitone.2. Glycine 13+/-2 nA and GABA 20+/-2 nA were equipotent depressors of hair cells (n=22) and, bicuculline applied by iontophoresis caused a parallel shift to the right of the GABA but not the glycine log-current response curves. The GABA equipotent dose-ratio was 2.0+/-0.2 for bicuculline currents of approximately 144 nA lasting about 11 min in cells excited either transynaptically by peripheral stimulation or postsynaptically by glutamate.3. Although a maximal bicuculline current seldom caused a significant shift of the glycine-log current response curve, many of our records show the onset of the glycine response to be slowed by doses in excess of 84 nA.4. Bicuculline also antagonized depressions by beta-guanidinopropionic acid, and delta-aminovaleric acid which mimicked the action of GABA.5. When tested on the same neurone, bicuculline and picrotoxin applied by iontophoresis were equipotent and their effects appear to be additive.6. The GABA sensitivity was not modified by repetitive (5 or 6) doses of i.v. bicuculline (0.2 mg/kg).7. The antagonism of GABA by bicuculline and picrotoxin appears to be of sufficient specificity to enable the separate roles of GABA and glycine as putative inhibitory transmitters of cuneo-thalamic relay cells to be determined.

Alkaloids↗
PubMed1973

On the pharmacology of the glycine receptors on the cuneo-thalamic relay cells in the cat.

1. In cats either decerebrated or anaesthetized with sodium pentobarbitone, strychnine released by iontophoresis from electrodes containing a 5 mM solution in 165 mM of NaCl, abolished the action of glycine and beta-alanine on cuneo-thalamic relay cells without disturbing their response to equally effective applications of gamma-aminobutyric acid (GABA) and beta-guanidino-propionic acid.2. The loss of glycine sensitivity appeared to increase as long as the strychnine release continued until even the largest currents tolerated by the electrode were unable to eject effective amounts of glycine. Parallel shifts of the glycine log-current response curves, equivalent to an equipotent dose-ratio of about 2.0 only occurred when the duration of the strychnine applications by current in excess of 28 nA was restricted to a few minutes.3. Without modifying either the frequency of the spike discharge or the amplitude or shape of the action potential, currents larger than 28 nA occasionally caused a loss of GABA sensitivity.4. Strychnine administered either intravenously (0.2 mg/kg) or applied topically to the surface of the cuneate (0.5 mM) blocked the response to glycine without any obvious effect on the response to GABA.5. It was concluded that the discovery of a strychnine-sensitive component of the inhibitory potentials recorded from the cuneate nucleus will reveal the physiological role of the glycine receptors on cuneo-thalamic relay cells.

Action Potentials↗
PubMed1973

On the pharmacology of ascending, decending and recurrent postsynaptic inhibition of the cuneo-thalamic relay cells in the cat.

1. In cats decerebrated or anaesthetized with pentobarbitone, cells of the middle third of the cuneate nucleus that were excited by tactile stimulation of the ipsilateral forelimb (responding to displacement of hairs, skin or joints) and inhibited by electrical stimulation of the contralateral pyramid, were invariably inhibited by electrical stimulation of the ipsilateral forepaw and the contralateral forelimb nerves.2. In 50% of the cats, the cells were more fully identified by placing electrodes stereotaxically in the contralateral medial lemniscus. Recurrent inhibition was always a concomitant of the antidromic action potential.3. The intensity and the duration of inhibition evoked by all of these pathways was totally resistant to iontophoretic and intravenous strychnine in doses at least 5 times that required to block completely the response of the same cells to iontophoretic glycine and was extremely sensitive to either iontophoretic bicuculline or picrotoxin.4. Although the inhibition was invariably sensitive to intravenous picrotoxin, no significant change occurred in the duration or intensity of the inhibition when bicuculline was administered intravenously (5 or 6 times) as repeated doses of 0.2 mg/kg.5. Postsynaptic inhibition in the cuneate may be mediated by gamma-aminobutyric acid released from the nerve terminals of a common pool of interneurones shared by ascending, descending and recurrent pathways. Since the receptors involved in this pathway are resistant to intravenous bicuculline, they may well be distinct from those responsible for changes in the primary afferent terminal excitability, usually believed to be associated with presynaptic inhibition.

Action Potentials↗
PubMed1972

Recurrent inhibition of antidromically identified rat supraoptic neurones.

1. In anaesthetized male rats, the hypothalamus and pituitary stalk were exposed by a transpharyngeal approach. The compound field potential of the supraoptic nucleus evoked by stimulation of the pituitary stalk, was recorded with glass electrodes inserted near the origin of the anterior cerebral artery.2. The mean latency of 169 antidromically evoked action potentials isolated from the field was 9.9 msec with an extreme range of 6-26 msec. Although the wave form of the antidromic action potential showed a variety of shapes and sizes and the initial wave could be of either polarity, the majority were strikingly similar in form. The initial wave was positive with an inflexion on the rising phase and was followed by a shallow rather longer lasting negative potential.3. The antidromic nature of the action potential was confirmed when the action potential evoked at constant latency after the stimulus was observed to be cancelled by another occurring spontaneously. Although the antidromic action potentials followed stimulation frequencies greater than 100 Hz, the response to high frequency stimulation was seldom tested since the amplitude of the action potential was greatly reduced at frequencies above 30 Hz if the number of shocks exceeded a critical number, as few as 3-6 at 100 Hz.4. Stimulation of the pituitary stalk at intensities below and near threshold for antidromic invasion of the cell under study was shown by means of post-stimulus time histograms to be associated with an inhibitory period lasting on average 80 msec (S.D. = 13, N = 30).5. An increase in the intensity and duration of the inhibitory period occurred as the intensity of the stimulation was increased as might be expected if the response was mediated synaptically. The inhibitory pathway is believed to involve the recurrent collateral axons already demonstrated anatomically since the stimulation intensities necessary to produce either a marked inhibitory response or antidromic invasion of the cell in question are in most instances nearly the same.

Action Potentials↗
PubMed1972

The activity of identified supraoptic neurones and their response to acetylcholine applied by iontophoresis.

1. In urethane/pentobarbitone anaesthetized male rats, the hypothalamus and pituitary stalk were exposed by a transpharyngeal approach. Cells recorded with glass micro-electrodes from the ventral hypothalamus near the bifurcation of the internal carotid artery were identified as supraoptic neurones only when their antidromic action potential evoked at constant latency by stimulation of the pituitary stalk was cancelled by collision with a spontaneously occurring action potential.2. More than 80% of the identified cells were spontaneously active. The frequency of firing was often slow (under 1 Hz) and rather irregular. More than half the cells, however, had a more distinctive firing pattern which recurred every 1-3 min and consisted of a period of low or absent activity alternating with periods of quite marked discharge which occasionally exceeded 20 Hz. This periodicity was retained when the over-all activity was enhanced by an intracarotid injection of 0.2 ml. 5% (w/v) NaCl.3. Of fifty-two cells tested, thirty-six were excited by acetylcholine applied by iontophoresis from a multibarrelled micropipette with average ejection currents of 35 +/- 5 nA (S.D. of thirty-six observations). Ten of these cells were also excited by nicotine applied with similar currents.

Acetylcholine↗
PubMed1971

Action potentials and release of neurohypophysial hormones in vitro.

1. Isolated rat neurohypophyses were studied in vitro and the hormones released on electrical stimulation of the pituitary stalk or on exposure to excess potassium were estimated by a milk-ejection assay.2. The stalk was stimulated with trains of 500 stimuli, or multiples thereof, applied at different frequencies. Below frequencies of ca. 35 c/s, hormone release was found to depend on the total number of stimuli applied as well as on the frequency of stimulation. Above ca. 35 c/s, identical numbers of stimuli were progressively less effective as the frequency of stimulation was increased, and the dependence of the hormone output on the total number of stimuli was less apparent.3. The amplitude of the compound action potential recorded from the neurohypophysis following electrical stimulation of the stalk was found to decrease as a function of the frequency of stimulation. Stimulation at 50 c/s reduced its amplitude about sevenfold within 30 sec.4. The addition of tetrodotoxin (TTX) to the incubation media abolished the compound action potential recorded from the neural lobe as well as the release of hormones evoked by electrical stimulation. Resting release, however, was unaffected by TTX.5. In TTX-treated neural lobes, excess potassium was still effective in eliciting graded secretory responses. This indicates the independence of the release process from the action potential generating mechanism and suggests that TTX-paralysed preparations represent a useful model for the study of hormone release in the absence of conducted action potentials.6. The release of hormones from the neurohypophysis and the release of neurotransmitters at chemical synapses both depend on the entry of calcium into the nerve terminals following their depolarization by invading action potentials. In both systems, experimental separation of the release mechanism can be achieved by the use of TTX. These and other parallels suggest that the release process is similar.

Action Potentials↗