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P Shinnick-Gallagher

Publications and source records attributed to P Shinnick-Gallagher.

At least 73 records · Page 4Linked to original sources
PubMed1984

alpha 2 and alpha 1-Adrenoceptors mediate opposing actions on parasympathetic neurons.

We used intracellular recording methods to analyze the membrane responses to norepinephrine in cat vesical parasympathetic ganglia. In parasympathetic neurons, norepinephrine (NE) produces a membrane hyperpolarization, a membrane depolarization often accompanied by cell firing and a biphasic potential, a hyperpolarization followed by a depolarization. We found that the NE hyperpolarization is mediated through alpha 2-adrenoceptors while the NE depolarization is mediated through alpha 1-adrenoceptors. This situation is different than in sympathetic neurons where beta-adrenoceptors mediate a NE depolarization.

Animals↗
PubMed1984

Intracellular recordings from rat dorsolateral septal neurons, in vitro.

We have made intracellular recordings from the dorsolateral septal nucleus (DLSN) in a rat brain slice. DLSN neurons fire short tetrodotoxin (TTX) sensitive action potentials followed by an after-hyperpolarization. The action potential is followed by either a Ca2+-dependent depolarization or a Ca2+-dependent after-hyperpolarization. Stimulation of medial septum results in antidromic invasion of DLSN neurons while stimulation of the fimbria/fornix results in orthodromic EPSPs or action potentials.

Action Potentials↗
PubMed1984

Slow excitatory post-synaptic currents in bull-frog sympathetic neurones.

Electrogenesis of the slow excitatory post-synaptic current (slow e.p.s.c.) was analysed with voltage-clamp methods in curarized sympathetic ganglion cells of bull-frogs. Three types of slow e.p.s.c. were observed from B neurones of sympathetic ganglia. The type I slow e.p.s.c. was associated with a decrease in membrane conductance, was depressed by membrane hyperpolarization and nullified at -60 to -70 mV. It was observed in 65% of the sympathetic neurones studied. The type II slow e.p.s.c. was associated with an increase in membrane conductance, was depressed by membrane depolarization and nullified at around +5 mV. It was observed in 14% of the neurones studied. A third type of slow e.p.s.c. was recorded from 21% of the sympathetic neurones in this study. This slow e.p.s.c. was a mixed type having characteristics of both type I and type II slow e.p.s.c.s. Activation of muscarinic cholinergic receptors by application of acetylcholine (ACh) also produced two types of inward currents. The nature of each type of muscarinic slow ACh current was similar to that of each type of slow e.p.s.c. The time course of the falling phase of type I and type II slow e.p.s.c.s was dependent on the membrane potential. The type I slow e.p.s.c. was primarily dependent on extracellular K+ and appeared to be produced by a suppression of the M-current (Brown & Adams, 1980). The type II slow e.p.s.c. was due to an increased conductance, probably to Na+, and other cations.

Acetylcholine↗
PubMed1983

The effects of temperature, pH and Cl-pump inhibitors on GABA responses recorded from cat dorsal root ganglia.

GABA applied by iontophoresis produced GABA-induced currents (GCs) and GABA-induced depolarizations (GDs) which were recorded intracellularly from cat dorsal root ganglia (DRG). Lowering the temperature (37 to 27 degrees C) of the preparation depressed the amplitude of GCs while prolonging their rise-time and decay time. This depressant action was mainly due to a hyperpolarizing shift in the GABA equilibrium potential (EGABA). GABA responses could also be depressed by alkalinization of the superfusion solution or addition of putative chloride pump inhibitors, e.g. SITS, furosemide or bumetanide. However, the mechanism by which these latter procedures depressed GABA responses was not due to a shift in EGABA as occurred with lowered temperature. Instead we suggest that alkalinization or the putative chloride pump inhibitors affect the chloride channel or some other site associated with the GABA receptor complex and cause the depression we observed. GABA responses could be facilitated by lowering the pH of the superfusion solution or by injecting ammonium ion into a DRG. These results suggest that a temperature-sensitive, inwardly directed chloride pump that is resistant to SITS, furosemide or bumetanide, operates in cat DRG.

4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfo↗
PubMed1983

On the mechanism of action of GABA in pelvic vesical ganglia: biphasic responses evoked by two opposing actions on membrane conductance.

Intracellular recording techniques were used to study the response of cat vesical pelvic ganglion neurones loaded with permeable anions to the application of GABA in vitro. In 106/127 neurones GABA evoked a biphasic response, the initial phase of which was depolarizing and associated with a conductance increase; the latter phase was hyperpolarizing and associated with a conductance decrease. The GABA evoked hyperpolarization and conductance decrease were related and behaved as though generated by closure of ion channels open in the resting membrane. The hyperpolarization had a strong inhibitory action on both spontaneous activity, and excitation evoked by depolarizing current injection and pre-synaptic nerve stimulation. Ion substitution experiments suggest that the conductance decrease is primarily to chloride ions, although other ionic species may contribute. Short iontophoretic applications of GABA-evoked monophasic depolarizing excitatory responses, even during the hyperpolarizing response evoked by perfusion of GABA, suggesting no cross-desensitization between the mechanisms generating the initial and late phases of the biphasic response.

Animals↗
PubMed1983

Effects of glial uptake and desensitization on the activity of gamma-aminobutyric acid (GABA) and its analogs at the cat dorsal root ganglion.

Responses to gamma-aminobutyric acid (GABA) and 13 structurally related analogs were recorded under voltage clamp conditions from isolated cat dorsal root ganglia (DRG). All of the analogs were applied by superfusion at a concentration of 1 mM. Of the 13 structurally related compounds, only muscimol was more effective than GABA in its ability to produce an inward current at the DRG membrane. Complete (1 microM-10 mM) concentration-response relationships were obtained for muscimol, GABA and 3-aminopropane sulfonic acid. Muscimol was most potent at all concentrations, however, the relative order of potency for GABA and 3-aminopropane sulfonic acid was concentration-dependent. In addition to producing differences in their peak currents, the various agonists demonstrated different time courses in their respective rates of decay. When the glial uptake system for GABA in cat DRG was inhibited by substituting lithium for sodium or by the addition of 1 mM nipecotic acid to the normal Krebs' solution, the membrane responses to GABA, SL-75102 and isoguvacine were facilitated, whereas the responses induced by the other analogs remained unchanged. Although the process of uptake altered significantly the decay phase of GABA responses when GABA was applied by superfusion or by iontophoresis, nipecotic acid inhibition of uptake did not appear to affect GABA-induced desensitization that was apparent when GABA was applied either by superfusion or with long iontophoretic pulses. GABA and all of the analogs in this study demonstrated cross-desensitization, each being able to depress the action of the other. Our results suggest that all of the active GABA analogs appear to be acting at a similar GABA receptor on cat DRG and this GABA receptor is coupled to a chloride channel.

Animals↗
PubMed1982

Morphine enhances and depresses Ca2+-dependent responses in visceral primary afferent neurons.

Morphine at 1 to 100 nM enhances and depresses Ca2+-dependent potentials, the shoulder of the action potential, the hyperpolarizing afterpotential, and the calcium spike in visceral primary afferent neurons of rabbits. These effects could be reversed by naloxone. The enhancement and depression of the Ca2+-dependent potentials are not only concentration-dependent but they are also time-dependent and can be observed with a given concentration of morphine.

Action Potentials↗
PubMed1982

Chemoreceptors for serotonin (5-HT), acetylcholine (ACh), bradykinin (BK), histamine (H) and gamma-aminobutyric acid (GABA) on rabbit visceral afferent neurons.

The somata of type 'C' neurons in rabbit nodose ganglion are endowed with receptor sites for 5-HT, BK, ACh, II and GABA. 5-HT and ACh application to type 'C' neurons in the nodose ganglion of rabbits produced a rapid depolarization associated with an increased membrane conductance, most likely to Na+ and K+. BK and H elicited slow depolarizations accompanied by a decreased membrane conductance probably to K+. GABA induced a rapid depolarization associated with an increased conductance to Cl-. In contrast, type 'A' neurons were insensitive to the four algesic agents but responded to GABA. d-Tubocurarine or picrotoxin at relatively low concentrations blocked ACh, 5-HT and GABA depolarizations without affecting membrane properties. Hexamethonium blocked ACh responses but not 5-HT responses. In addition, no desensitization occurred between the substances 5-HT, ACh or BK. The results suggest that the depolarizing effect of these agents on visceral neurons might be exerted via different receptors.

Acetylcholine↗
PubMed1982

Cholinergic transmission in cat parasympathetic ganglia.

1. Intracellular electrical recording techniques were used to study the ionic mechanisms of cholinergic synaptic transmission in cat vesical pelvic ganglia (v.p.g.). 2. Orthodromic nerve stimulation as well as ionophoretic application of acetylcholine (ACh) resulted in, first, a fast excitatory post-synaptic potential (f.e.p.s.p.) and secondly, a slow inhibitory post-synaptic potential (s.i.p.s.p). These distinct post-synaptic responses were direct actions of ACh and not mediated through an interneurone. In addition, a slow excitatory post-synaptic potential (s.e.p.s.p.) was observed in 44% of the cells. 3. The f.e.p.s.p., mediated via nicotinic receptors, had a reversal potential of -10 mV and resembled the conventional rapid depolarization in other ganglia. The s.i.p.s.p., mediated by muscarinic receptors, had a reversal potential of about -100 mV and resulted from an increase in potassium conductance. 4. The slow muscarinic hyperpolarization could be observed in the absence of antagonists and it was elicited at stimulus frequencies in the physiological range (2-10 Hz). the s.i.p.s.p. induced orthodromically or ionophoretically inhibited firing in spontaneously active neurones. These observations suggest that the muscarinic hyperpolarization may occur under physiological conditions and has sufficient magnitude to be inhibitory to neuronal activity.

Acetylcholine↗
PubMed1981

Sucrose-gap recordings of nerve-evoked potentials in mammalian parasympathetic ganglia.

The sucrose-gap recording technique was used to study mammalian parasympathetic ganglionic transmission. Both a fast nicotinic depolarization potential and a slow muscarinic hyperpolarizing potential were recorded in vesical pelvic ganglia (VPG). A long afterhyperpolarization caused by an electrical response of through-fibers was also recorded. However, a slow excitatory postsynaptic potential (S-EPSP) was not readily observed and may be masked by the long afterhyperpolarization. In addition, the slow inhibitory postsynaptic potential (S-IPSP) of the VPG was due to a direct effect of acetylcholine (ACh). Thus, sucrose-gap recordings of VPG potentials are similar to those obtained in sympathetic ganglia, but the mechanism for transmission of the S-IPSP may be different in the respective ganglia.

Acetylcholine↗
PubMed1981

Spinal sympathetic reflex and random activity in the isolated amphibian spinal cord.

Preganglionic sympathetic neurons in the fourth ramus communicantes discharged in response to electrical stimulation of somatic or visceral afferents entering the spinal cord at segments 2, 3, or 4. Intrasegmental reflexes consisted of a large peak followed by a second, smaller one, whereas only a single peak was observed in intrasegmental reflex. Reflex wave forms were similar to those in the cats except a monosynaptic component was not usually observed. In addition latencies and central delays were different in frogs and cats. Spontaneous activity was rarely recorded although poststimulus random activity was usually observed. Medium to high threshold afferents were responsible for eliciting spinal sympathetic reflexes from spinal nerve two. In frogs the interaction between spinal sympathetic reflexes elicited by the same or different afferents was qualitatively similar to that in cats. It appears therefore that the amphibian spinal cord is a suitable preparation for analyzing sympathetic preganglionic neurons.

Action Potentials↗
PubMed1981

Catecholamine modulation of spinal sympathetic reflexes.

Sympathetic reflexes in an in vitro frog spinal cord appeared to be qualitatively similar to those observed in cats in vivo. The present study ws conducted to determine whether or not this similarity extended to catecholamine effects on spinal sympathetic reflexes and to examine the adrenoceptor mechanisms responsible for these effects. Norepinephrine inhibited spinal sympathetic reflexes elicited by supramaximal electrical stimulation of the second spinal nerve in a concentration-dependent manner. This inhibition could be mimicked by other alpha adrenoceptor agonists and was antagonized by phentolamine. No effect of norepinephrine was observed when submaximal stimuli were employed. Epinephrine facilitated reflex activity elicited by both submaximal and supramaximal stimulation; however, in the presence of propranolol, an inhibitory effect of epinephrine was observed. At high concentrations, dopamine inhibited spinal sympathetic reflex activity and this inhibition was antagonized by phentolamine. l-Dopa produced a slow-onset, long-lasting inhibition which could be blocked by pretreatment with a decarboxylase inhibitor. It is concluded that alpha adrenoceptor agonists acting on alpha receptors can inhibit spinal sympathetic reflex activity and that the inhibition is dependent on the intensity of stimulation. Activation of beta adrenoceptors facilitates, whereas activation of dopamine receptors has no effect on, spinal sympathetic reflexes. These alpha and beta adrenoceptor mechanisms may function in the modulation of sympathetic preganglionic activity in the intact animal.

Adrenergic alpha-Agonists↗
PubMed1981

Comparison of the receptors mediating the catecholamine hyperpolarization and slow inhibitory postsynaptic potential in sympathetic ganglia.

We investigated the proposed catecholamine receptor in the superior cervical ganglion of the rabbit with the sucrose-gap technique to characterize the receptor pharmacologically. It has been suggested that this receptor is involved in the slow inhibitory postsynaptic potential in sympathetic ganglia. Epinephrine, norepinephrine and dopamine consistently hyperpolarized the ganglion membrane (N = 60). The order of potency was epinephrine greater than or equal to norepinephrine much greater than dopamine. Clonidine (10(-5) M), phenylephrine (10(-4) M) and isoproterenol (10(-3) M) also hyperpolarized the ganglion. However, apomorphine, even at millimolar concentration, did not hyperpolarize the membrane. The alpha antagonists phentolamine (10(-6) M) and yohimbine (10(-6) M) depressed the response to all catecholamines and shifted the catecholamine concentration-response curve to the right; dopamine and beta antagonists and the alpha-1 antagonist prazosin had no effect on the catecholamine hyperpolarizations. In contrast, the nerve-evoked slow inhibitory postsynaptic potential was selectively depressed only by atropine (10(-7) M). In conclusion, we characterized an alpha-2 adrenergic receptor in the rabbit superior cervical ganglion responsible for the catecholamine hyperpolarization and found that the slow inhibitory postsynaptic potential does not appear to be mediated by the same receptor.

Adrenergic alpha-Antagonists↗
PubMed1980

Dopamine depolarisation of mammalian primary afferent neurones.

Dopamine (DA) is an important neurotransmitter or neuromodulator in the mammalian nervous system. As such, it is implicated in the aetiology and therapy of various disease conditions--for example, Parkinson's disease, schizophrenia, Huntington's disease and tardive dyskinesia. However, only limited electrophysiological information is presently available concerning dopamine receptors in the mammalian nervous system, and there are only three reports in which intracellular techniques have successfully recorded the action of DA on individual central neurones. In all cases, DA depolarised the respective neurones. In the periphery, DA is reported to hyperpolarise superior cervical ganglia. However, this hyperpolarisation has been shown to be due to activation of alpha-adrenoreceptors and not to a response of DA on a DA receptor. Peripheral DA actions have also been described presynaptically, but are difficult to study electrophysiologically for technical reasons. As a result, little is known at the membrane level about the effects of drugs thought to modulate or interact with DA receptors. In the present report, we describe a depolarising action for DA on the cat dorsal root ganglion.

Afferent Pathways↗
PubMed1980

Effect of Gymnodinium breve toxin in the rat phrenic nerve diaphragm preparation.

1 The effects of a crude fraction of Gymnodinium breve toxin (GBTX) were studied on the rat phrenic nerve diaphragm preparation. 2 Indirectly stimulated muscle contractions were more sensitive to blockade by increasing concentrations of GBTX (0.25 microgram/ml to 10 micrograms/ml) than direct muscle contractions. 3 GBTX increased miniature endplate potential (m.e.p.p.) frequency and depolarized the resting membrane potential of the muscle fibres at the endplate and in non-synaptic regions of muscle fibre. 4 A concentration-dependent biphasic effect on m.e.p.p. amplitude was evident. At lower concentrations m.e.p.p. amplitudes were depressed whereas at high concentrations they were increased. 5 GBTX blocked endplate potentials (e.p.ps) in concentrations (0.5 microgram/ml to 2 micrograms/ml) that did not block m.e.p.ps. 6 Muscle fibre action potentials recorded from cells held at control membrane potential by hyperpolarizing current were not altered by toxin treatment. No repetitive e.p.ps, or muscle action potentials were observed. 7 These data suggest that GBTX may block indirectly stimulated muscle contractions and e.p.ps by depolarizing the nerve terminal in a manner similar to the observed depolarization of the muscle fibre. The depolarization of the nerve terminal may be sufficient to inhibit transmitter release.

Action Potentials↗