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N J Dun

Publications and source records attributed to N J Dun.

At least 127 records · Page 7Linked to original sources
PubMed1984

Slow non-cholinergic excitatory potentials in neurones of the guinea-pig coeliac ganglia.

Intracellular recordings were made from neurones of the coeliac ganglia of the guinea-pig in vitro. In addition to the fast excitatory post-synaptic potential (e.p.s.p.) repetitive stimulation (10-20 Hz, 1-2 s) of the left greater splanchnic nerves elicited a slow depolarization in about 70% of the neurones examined. This depolarization lasted for minutes and was resistant to nicotinic and muscarinic antagonists; it was abolished reversibly in a low-Ca2+, high-Mg2+ solution. The response is henceforth termed non-cholinergic e.p.s.p. In about 10% of the neurones the non-cholinergic e.p.s.p. exhibited a biphasic pattern. The fast as well as the non-cholinergic e.p.s.p. could be effectively induced by stimulation of any of the several nerve trunks that enter the ganglion. Moreover, simultaneous stimulation of two separate nerves resulted in a much larger non-cholinergic e.p.s.p. than could be achieved by stimulation of a single nerve. When the membrane potential was manually clamped, the non-cholinergic e.p.s.p. was associated with an increase of membrane resistance in the large majority of cells tested. Membrane hyperpolarization generally caused an increase in the amplitude of the non-cholinergic e.p.s.p.; a decrease was observed in only a few cells. Subthreshold depolarizations induced by direct intracellular stimulation as well as fast e.p.s.p.s elicited by heterosynaptic nerve stimulation were facilitated during the course of a non-cholinergic e.p.s.p., often resulting in spike discharges. A potentiation of lesser magnitude occurred when the membrane potential was manually clamped during the course of the slow response, indicating that the facilitation may be attributed to both membrane depolarization and increased membrane resistance. These results indicate that the non-cholinergic e.p.s.p. constitutes an integral part of synaptic transmission in coeliac ganglia, and that its function may be to provide a mechanism for increasing the responsiveness of sympathetic neurones to incoming fast e.p.s.p.s.

Action Potentials↗
PubMed1984

Evidence for a serotonin-mediated slow excitatory potential in the guinea-pig coeliac ganglia.

The nature of the putative transmitter(s) mediating the non-cholinergic excitatory post-synaptic potential (e.p.s.p.) described in the preceding paper was investigated by means of electrophysiological, pharmacological and immunohistochemical methods. Serotonin (1-10 microM) when applied by superfusion caused a slow depolarization that closely mimicked the synaptic response in about 60% of the coeliac neurones that exhibited a non-cholinergic e.p.s.p. The serotonin depolarization evoked in low-Ca2+, high-Mg2+ solution or in a Krebs solution containing cholinergic antagonists was quantitatively similar to that elicited in normal Krebs solution. When compared in the same neurones the membrane resistance change during the course of the serotonin depolarization and of the non-cholinergic e.p.s.p., as well as their respective responses to conditioning polarization, were similar. The non-cholinergic e.p.s.p. was reversibly abolished during serotonin-induced depolarization; the blockade persisted when the membrane potential was restored to the resting level by hyperpolarizing current. The serotonin depolarization as well as the non-cholinergic e.p.s.p. were reversibly suppressed by cyproheptadine (20-50 microM), a serotonin antagonist, and enhanced by fluoxetine (30-50 microM), a serotonin reuptake inhibitor. On the other hand, pre-treating the ganglia with L-tryptophan (50 microM), a precursor of serotonin, preferentially augmented the synaptically induced response. A portion of the neurones (15%) were depolarized by substance P (1 microM) which also reversibly desensitized the non-cholinergic e.p.s.p. elicited in these neurones. The remaining neurones (25%) were insensitive to either serotonin or substance P, and the non-cholinergic e.p.s.p.s elicited in these cells were likewise not appreciably affected by these two agents. Furthermore, cyproheptadine, fluoxetine and L-tryptophan had no significant effect on the non-cholinergic e.p.s.p.s elicited in serotonin-insensitive neurones. Using the immunohistofluorescent techniques, dense but unevenly distributed serotonin immunoreactive nerve fibres could be observed surrounding many coeliac neurones. Immunoreactivity was not observed in the ganglia incubated with antisera pre-absorbed with excess serotonin. Collectively our results suggest that serotonin is the mediator of non-cholinergic e.p.s.p.s. elicited in about 60% of coeliac neurones sampled in this study, and that in the remaining neurones the slow depolarization may be generated by substance P and/or some unknown transmitter(s).

Action Potentials↗
PubMed1984

Long-term facilitation of peptidergic transmission by catecholamines in guinea-pig inferior mesenteric ganglia.

Intracellular recordings were obtained from neurones of isolated guinea-pig inferior mesenteric ganglia. Repetitive stimulation (10-20 Hz for 1-2 s) of the hypogastric nerves evoked, in addition to the fast excitatory post-synaptic potential (e.p.s.p.), a non-cholinergic e.p.s.p. the mediator of which has previously been suggested to be substance P or a related peptide. When applied to the ganglia in the concentrations of 1-100 microM for 3-5 min, adrenaline, isoprenaline and noradrenaline produced an initial, short-lasting depression which was followed by a marked augmentation of the non-cholinergic e.p.s.p. lasting from minutes to over hours. Employed in comparable concentrations dopamine caused a slight depression that was not followed by a detectable increase of the non-cholinergic e.p.s.p. The catecholamine-induced depression and subsequent enhancement of the non-cholinergic e.p.s.p. was prevented by alpha-adrenergic antagonists (dihydroergotamine and phenoxybenzamine, 1-10 microM) and beta-adrenergic antagonists (propranolol and dichlorisoprenaline, 5-10 microM), respectively. The membrane depolarization induced by the putative transmitter substance P (1 microM) was augmented by isoprenaline; the enhancement which could be blocked by beta-antagonists was not preceded by a depression. Application of dibutyryl cyclic AMP (10 microM-1 mM) by either superfusion or intracellular ionophoresis mimicked the enhancing effect of catecholamines. It is concluded that catecholamines, with the noticeable exception of dopamine, exerted a biphasic effect on the non-cholinergic e.p.s.p. of the inferior mesenteric ganglion cells: an initial depression that was mediated by alpha-adrenergic receptors and probably reflected a presynaptic inhibitory effect of catecholamines and, on the other hand, an enduring facilitation mediated by beta-adrenergic receptors which appeared to be linked to activation of post-ganglionic cyclic AMP.

Action Potentials↗
PubMed1983

Serotonin mediates a slow excitatory potential in mammalian celiac ganglia.

Neuropharmacological and histochemical evidence presented here indicates that serotonin (5-HT) is the transmitter mediating one of the postsynaptic potentials in the guinea pig celiac ganglion. Repetitive nerve stimulation elicited in celiac neurons, in addition to the nicotinic fast excitatory postsynaptic potential (EPSP), a slow EPSP that was resistant to cholinergic antagonists. Application of 5-HT caused a depolarization with membrane characteristics similar to those of the slow EPSP; furthermore, the latter was reversibly suppressed by 5-HT. The slow depolarization evoked by either nerve stimulation or 5-HT was augmented by fluoxetine, a 5-HT reuptake blocker, and depressed by cyproheptadine, a 5-HT receptor blocker; in addition, tryptophan, a precursor of 5-HT, enhanced differentially the slow EPSP. Lastly, histochemical study revealed dense networks of 5-HT immunoreactive nerve fibers encircling many ganglionic neurons.

Action Potentials↗
PubMed1983

Evidence of slow IPSP in mammalian prevertebral ganglia.

A short train of nerve stimulation evoked in a portion of neurons of the guinea pig inferior mesenteric ganglia a slow hyperpolarization (slow IPSP) which persisted when the preceding orthodromic spikes were reduced to subthreshold EPSPs by curare, was reversibly abolished in a low Ca solution, and was not blocked by atropine; furthermore, the post-tetanic hyperpolarization induced by direct intracellular stimulation was generally smaller than the slow IPSP evoked by nerve stimulation. The slow IPSP was often associated with a fall in membrane resistance and its amplitude decreased with membrane hyperpolarization. The results indicate that the slow hyperpolarization is a synaptic potential, and differs from the slow IPSP observed in mammalian and amphibian paravertebral ganglionic neurons in that it is atropine insensitive.

Animals↗
PubMed1983

Capsaicin causes release of a substance P-like peptide in guinea-pig inferior mesenteric ganglia.

The effects of capsaicin (0.5-100 microM) on neurones of the isolated inferior mesenteric ganglia (i.m.g.) of the guinea-pig were investigated by means of intracellular recording techniques. When applied to neurones of the i.m.g. that exhibited a slow non-cholinergic excitatory potential (Dun & Jiang, 1982), capsaicin caused in the large majority of these cells a long lasting depolarization accompanied by intense neuronal discharges. During and immediately following the depolarization, repetitive presynaptic stimulation consistently failed to elicit the non-cholinergic depolarization; a partial recovery was observed in relatively few neurones. The fast (nicotinic) excitatory post-synaptic potentials (e.p.s.p.s) were not suppressed by capsaicin in any of these cells. The membrane potential, input resistance and the amplitude of fast e.p.s.p.s in neurones of the i.m.g. that generated no detectable non-cholinergic depolarizations were not affected by capsaicin. Post-synaptic membrane sensitivity to exogenous application of substance P was not altered following capsaicin superfusion even though the latter effectively abolished the non-cholinergic depolarization in the same neurones. Superfusing the i.m.g. with a Ca-free Krebs solution markedly attenuated or abolished the depolarizing effect of capsaicin whereas tetrodotoxin (1 microM) was without effect. Capsaicin was without effect in a few neurones that generated a non-cholinergic depolarization; the latter was not desensitized by bath application of substance P. Capsaicin caused no appreciable effects in neurones of the bullfrog sympathetic ganglia; thus, the fast and slow post-synaptic potentials including the late slow e.p.s.p. the transmitter of which is the peptide luteinizing hormone-releasing hormone (Jan & Jan, 1982) were not affected. The results suggest that the depolarizing effect of capsaicin in neurones of the guinea-pig i.m.g. is due to a selective release of ganglionic substance P or a substance P-like peptide in a Ca-dependent manner, and that the non-cholinergic potentials elicited in capsaicin-insensitive neurones may be generated by a transmitter(s) other than substance P.

Action Potentials↗
PubMed1982

Substance P: a putative sensory transmitter in mammalian autonomic ganglia.

Repetitive presynaptic stimulation elicited slow membrane depolarization in neurons of inferior mesenteric ganglia from guinea pigs. This response was not blocked by cholinergic antagonists but was specifically and reversibly inhibited by a substance P analog, (D-Pro2, D-Phe7, D-Trp9)-substance P, which also depressed the depolarization induced by exogenously applied substance P. The atropine-sensitive slow excitatory and slow inhibitory postsynaptic potentials evoked in neurons of rabbit superior cervical ganglia were not affected by the substance P analog. These and previous results provide strong support for the hypothesis that substance P or a closely related peptide is the transmitter mediating the slow depolarization. The latter may represent a sensory input from the gastrointestinal tract to neurons of the prevertebral ganglia.

Action Potentials↗
PubMed1982

Enkephalinergic modulation of non-cholinergic transmission in mammalian prevertebral ganglia.

The non-cholinergic excitatory potential elicited in neurons of the isolated inferior mesenteric ganglia was depressed by bath application of Met- or Leu-enkephalin and enhanced by naloxone or naltrexone. The membrane depolarization induced by exogenously applied putative transmitter substance P was not appreciably affected by either enkephalin (Enk) or opiate antagonists. Our results indicate that the non-cholinergic excitatory transmission which may be mediated by substance P in prevertebral ganglia is modulated presynaptically by endogenously released Enk in a manner that may resemble the interaction between these two peptides in the spinal cord.

Animals↗
PubMed1982

Post-tetanic depolarization in sympathetic neurones of the guinea-pig.

1. Repetitive intracellular stimulation at a frequency of 5-30 Hz for 1-10 s evoked in neurones of the isolated inferior mesenteric and superior cervical ganglia of the guinea-pig three types of post-spike membrane potential changes: (i) hyperpolarization, (ii) hyperpolarization followed by a slow depolarization, and (iii) a second hyperpolarization following the initial two responses.2. The initial post-spike hyperpolarization had a mean duration of 2.0 s and was often associated with a fall in membrane resistance; it could be elicited in every sympathetic neurone studied. This response was termed the post-tetanic hyperpolarization (PTH).3. The slow depolarization which could be induced only in a portion of neurones had a mean amplitude and duration of 2.2 mV and 27.5 s, respectively; it was termed the post-tetanic depolarization (PTD).4. PTD was associated with a fall in membrane resistance, augmented by membrane hyperpolarization, and reduced by depolarization; its mean extrapolated equilibrium potential was -38 mV.5. PTD was not blocked by nicotinic and muscarinic antagonists, or alpha-and beta-adrenergic receptor antagonists, whereas it was suppressed by adrenaline, noradrenaline, Co(2+) and a low Ca(2+) solution.6. The amplitude of the single spike after-hyperpolarization in normal Krebs solution as well as in high K(+) solution was increased during PTD; furthermore, conditioning hyperpolarization to the level of E(K) increased the amplitude of PTD in normal Krebs as well as in high K(+) solution.7. PTD with similar amplitude, time course and membrane characteristics could be evoked in a portion of neurones of the rabbit superior cervical ganglia; however, PTD was not detected in neurones of the rat superior cervical ganglia.8. Decentralization of the guinea-pig and rabbit superior cervical ganglia for 14 d did not alter the number of neurones in which PTD could be elicited, its amplitude, or its time course.9. Our results suggest that a chemical substance(s) is responsible for the generation of PTD; it may be released from the soma and/or dendrites and acts in an auto-receptive manner on the cells in question. The nature and origin of the second hyperpolarization remain to be clarified.

Action Potentials↗
PubMed1982

Non-cholinergic excitatory transmission in inferior mesenteric ganglia of the guinea-pig: possible mediation by substance P.

1. Repetitive stimulation of guinea-pig hypogastric nerves elicited, in addition to the fast cholinergic excitatory potential, a slow depolarization lasting for seconds to minutes in neurones of the isolated inferior mesenteric ganglion. 2. The slow depolarization which could be elicited at a frequency as low as 1-2 Hz for several seconds was not blocked by cholinergic antagonists, but was eliminated in a low Ca2+ solution; it was termed henceforth the non-cholinergic excitatory potential. 3. When the membrane potential was manually clamped, the non-cholinergic potential was associated with three types of membrane resistance change: an increase, a delayed increase and a biphasic change consisting of an initial decrease followed by an increase. 4. In the majority of neurones, conditioning hyperpolarization augmented the non-cholinergic depolarization; in a few neurones, moderate hyperpolarization depressed the latter, whereas stronger hyperpolarization unmasked a low depolarization. 5. The non-cholinergic response was markedly attenuated in the presence of exogenously applied substance P; it was partially suppressed by luteinizing hormone-releasing hormone. 6. Non-cholinergic depolarization could be elicited in the same neurone by stimulation of all four nerve trunks associated with the ganglion. 7. It is suggested that substance P, a peptide, may be the transmitter responsible for the generation of the non-cholinergic potential and that it may be released from collateral endings of primary sensory neurones, thus providing a functional connexion between sensory and autonomic neurones.

Acetylcholine↗
PubMed1981

Multiple conductance change associated with the slow excitatory potential in mammalian sympathetic neurons.

When the membrane potential was manually clamped, the non-cholinergic excitatory potential was associated with either a sustained increase, an initial decrease followed by a prolonged increase or no apparent change in neuronal input resistance. In the majority of neurons studied, the amplitude of non-cholinergic depolarization was augmented upon conditioning hyperpolarization, whereas it was attenuated in a low Na solution. The results are consistent with the suggestion that the non-cholinergic depolarization may be generated by a change of multiple conductances that may include GNa activation and GK inactivation.

Adrenergic Fibers↗
PubMed1981

Substance P-induced depolarization in sympathetic neurons: not simple K-inactivation.

Ionic mechanisms underlying substance P-induced depolarization of the inferior mesenteric ganglion cells of the guinea pig were analyzed by means of microelectrode methods. When the membrane potential was manually clamped at the resting level, substance P caused, in about equal number of neurons, increases and decreases of neuronal input resistance. In the majority of the cells tested the amplitude of substance P-induced depolarization was increased when the membrane was hyperpolarized to the level of EK; it was markedly reduced in a Na+-free media. These results suggest that substance P causes depolarization by simultaneously increasing Na+ and decreasing K+ permeability.

Animals↗
PubMed1981

Effects of substance P on neurones of the inferior mesenteric ganglia of the guinea-pig.

1. The membrane effects of substance P on neurones of isolated inferior mesenteric ganglia and the underlying ionic mechanisms were investigated by means of intracellular recording techniques.2. When applied to the neurones by superfusion, substance P (0.5 mum) caused a membrane depolarization; in a few neurones, the depolarization was preceded by a small hyperpolarization. Substance P effects were not altered in a low Ca(2+)/high Mg(2+) solution or in a solution containing d-tubocurarine and atropine.3. When the membrane potential was clamped manually at the resting level between -50 and -60 mV, substance P caused, in about an equal number of neurones, a slight to moderate decrease and also increase of membrane resistance; a brief increase occurred prior to the decrease of membrane resistance.4. In neurones with high resting membrane potential (> -70 mV), substance P elicited a large depolarization accompanied by a marked increase in membrane resistance; the latter was probably due to anomalous rectification.5. Conditioning hyperpolarization of the membrane close to the level of E(K) increased and decreased substance P-induced depolarization in eleven and two neurones, respectively.6. Substitution of external Na(+) with an equimolar amount of either sucrose or Tris buffer markedly attenuated the depolarizing effect of substance P.7. The substance P-induced depolarization was diminished in a high K(+) (10 mm) solution, and it could be augmented when membrane was hyperpolarized to E(K). On the other hand, the effect of substance P was not appreciably affected in a low Cl(-) solution.8. It is concluded that substance P depolarizes the sympathetic neurones by increasing and decreasing membrane permeability to Na(+) and K(+), respectively, and that the concomitant membrane resistance change depends on interaction of G(Na) activation and G(K) inactivation.9. The possibility that substance P is the transmitter mediating the non-cholinergic slow excitatory potential elicited by repetitive preganglionic stimulation in the neurones of the inferior mesenteric ganglia is suggested.

Animals↗
PubMed1981

Evidence for a presynaptic inhibitory action of 5-hydroxytryptamine in a mammalian sympathetic ganglion.

Effects of 5-hydroxytryptamine (5-HT) on synaptic transmission of isolated rabbit superior cervical ganglia were investigated by means of intracellular recording techniques. Superfusion of 5-HT (1-100 microM) onto the ganglion cells reversibly depressed the amplitude of the fast excitatory postsynaptic potential (epsp) without causing a noticeable change in the membrane potential or input resistance in the majority of cells studied. In a portion of neurons, 5-HT produced a small to moderate, transient depolarization accompanied by a fall in membrane resistance, as well as a diminution of the epsp. In these neurons, the synaptic potentials did not recover to their full amplitude even when the membrane potentials and membrane resistance had returned to the control level. The inhibitory effect of 5-HT was not antagonized by lysergic acid diethylamide (0.3-1 microM), methysergide (1-10 microM), picrotoxin (10-50 microM) and phenoxybenzamine (5 microM); the first two agents when applied alone reversibly diminished the epsp. The mean quantal content but not the quantal size of the evoked epsp was significantly reduced by 5-HT in a low Ca/high Mg solution. Lastly, 5-HT reduced the amplitude of epsp while not appreciably affecting the acetylcholine potential induced by iontophoresis of the acetylcholine onto the same ganglion cells. These results provide electrophysiological evidence suggesting that 5-HT-induced inhibition of synaptic transmission in sympathetic ganglia is primarily due to a presynaptic mechanism resulting in a reduction of the evoked release of acetylcholine.

Acetylcholine↗
PubMed1980

A light and electron microscopic study of the rat superior cervical ganglion cells by intracellular HRP-labeling.

Horseradish peroxidase (HRP) was injected intracellularly into single neurons of the isolated rat superior cervical ganglia. Intracellular iontophoresis of HRP did not seem to damage the sympatheticneurons or to affect synaptic transmission. Under the light microscope, 9 of the 27 HRP-labeled sympathetic neurons exhibited varicosities in their dendrites, but not in their axons; the varicose dendrites came into close contacts with adjacent non-labeled neurons. With the electron microscope, the varicose dendrites of 3 separate neurons lightly stained with HRP, morphological features of synapses could be identified at the contact site: clusters of vesicles in the varicose dendrites, intercellular space of about 20 nm separating the apposed membranes, and an intermediate density on the postjunctional membrane. These findings suggest at the ultrastructural level the occurrence of dendrodendritic and dendro-somatic synapses in mammalian sympathetic ganglia.

Animals↗