Biomedical subjects

N J Dun

Publications and source records attributed to N J Dun.

At least 109 records · Page 6Linked to original sources

PubMed1987

Excitatory postsynaptic potentials in neonatal rat sympathetic preganglionic neurons: possible mediation by NMDA receptors.

Excitatory postsynaptic potentials (EPSPs) evoked in antidromically identified sympathetic preganglionic neurons (SPNs) and membrane depolarizations induced by N-methyl-D-aspartate (NMDA) applied by pressure ejection were increased by removing Mg ions from the perfusing media and blocked by D-2-amino-5-phosphonovalerate (APV), DL-APV and ketamine. Further, the amplitude of EPSPs and NMDA-induced depolarizations were decreased and increased by membrane hyperpolarization in Krebs solution with and without Mg2+, respectively. These findings indicate that the excitatory amino acid receptor mediating the EPSPs in SPNs may be of the NMDA subtype.

Animals↗

PubMed1987

Is glycine an inhibitory transmitter in rat lateral horn cells?

Spontaneous inhibitory postsynaptic potentials (IPSPs) and evoked IPSPs were recorded from a portion of lateral horn cells situated in thin transverse thoracolumbar spinal cord slices removed from neonatal rats. The IPSPs were reduced by hyperpolarization and inverted at membrane potentials between -65 and -75 mV. Strychnine but not bicuculline reversibly eliminated the IPSPs. The hyperpolarizations elicited by exogenously applied glycine exhibited electrophysiological and pharmacological characteristics similar to that of IPSPs. The results are consistent with the suggestion that glycine mediates an IPSP in a population of lateral horn cells.

Animals↗

PubMed1987

Fast and slow depolarizing responses of guinea-pig coeliac ganglion cells to 5-hydroxytryptamine.

Responses to 5-hydroxytryptamine (5-HT) applied by pressure ejection to guinea-pig coeliac ganglion cells were recorded intracellularly in vitro. Three types of responses were observed: a fast depolarization (43% of cells), a slow depolarization (25%) and a biphasic response comprising an initial fast followed by a slow depolarization (30%). Fast depolarizations had a mean duration of 6.4 s and were associated with a decrease in membrane input resistance. On hyperpolarizing the membrane, responses increased in amplitude; the mean reversal potential was -23 mV. Fast responses were nearly eliminated in a Na-free medium but were unaffected by low Ca/high Mg solution or by low Cl medium. Fast responses were depressed by MDL 72222, quipazine, metoclopramide, and by relatively high concentrations of D-tubocurarine, but unaffected by methysergide. Slow responses had a mean duration of 62 s and were associated either with no change or a slight fall in membrane resistance. hyperpolarizing the membrane, slow responses were increased in most but not all cells tested. Slow depolarizations were depressed by methysergide but unaffected by agents that suppressed the fast responses. The biphasic response displayed electrophysiological and pharmacological characteristics of both the fast and slow depolarizations. It is concluded that guinea-pig coeliac ganglion cells display either a rapid depolarization, a slow depolarization or a biphasic response to 5-HT, that the fast depolarization appears to be mediated by a conductance increase to Na and K, while a different mechanism appears to underlie the slow depolarization, and that the two responses are mediated by different kinds of 5-HT receptor.

Animals↗

PubMed1987

Neurokinin A in capsaicin-sensitive neurons of the guinea-pig inferior mesenteric ganglia: an additional putative mediator for the non-cholinergic excitatory postsynaptic potential.

The presence of neurokinin-A-like immunoreactivity in guinea-pig inferior mesenteric ganglia was detected by radioimmunoassay procedures. Pretreating the animals with capsaicin 7 days prior to experimentations reduced the mean content of neurokinin-A-like immunoreactivity by 85% from its control value of 150 +/- 31.3 fmol per ganglion. High-performance liquid chromatography revealed that neurokinin-A-like immunoreactivity was heterogenous as in addition to neurokinin A, peaks corresponding to the amphibian tachykinin eledoisin and to neuropeptide K were detected, and they too were depleted by capsaicin. Electrophysiological studies showed that neurokinin A applied either by superfusion or by pressure ejection evoked a slow depolarization in the majority of inferior mesenteric ganglia neurons in vitro. Neurokinin-A-evoked depolarizations in the majority of cells tested were associated with a small increase in membrane input resistance. However, the responses were increased by membrane hyperpolarization: the extrapolated mean equilibrium potential of neurokinin-A-induced depolarization was -36 mV. Removal of extracellular sodium but not chloride ions suppressed the neurokinin-A-induced depolarization. The slow depolarization elicited either by exogenously applied substance P or by repetitive stimulation of hypogastric nerves was reversibly eliminated in the presence of neurokinin A. Collectively, our studies suggest that neurokinin-A-like immunoreactivity may coexist with substance-P-like immunoreactivity in capsaicin-sensitive fibers in the guinea-pig prevertebral ganglia and that the similarity of the actions of neurokinin A on the one hand and substance P on the other raises the possibility that non-cholinergic excitatory potentials elicited in the inferior mesenteric ganglia may be generated by not one but a number of closely related tachykinins.

Animals↗

PubMed1986

Presynaptic suppression of excitatory postsynaptic potentials in rat ventral horn neurons by muscarinic agonists.

In addition to depolarizing the ventral horn cells including antidromically identified motoneurons in thin transverse neonatal rat spinal cord slice preparations, exogenously applied acetylcholine (ACh) suppressed the amplitude of excitatory postsynaptic potentials (EPSPs) either occurring spontaneously or elicited by stimulation of dorsal rootlets. A reduction of EPSPs could still be detected when the ACh-induced depolarization was nullified by hyperpolarizing current. Atropine but not D-tubocurarine effectively antagonized the depolarization and synaptic depression caused by ACh. While depressing the EPSPs, ACh had no appreciable effect on membrane depolarizations elicited by glutamate. Methacholine mimicked the depolarizing and synaptic depressant effects of ACh. The results suggest that muscarinic agonists inhibit synaptic transmission of ventral horn neurons including motoneurons by a presynaptic mechanism in reducing the output of excitatory transmitters.

Acetylcholine↗

PubMed1986

Cholecystokinin octapeptide depolarizes guinea pig inferior mesenteric ganglion cells and facilitates nicotinic transmission.

Cholecystokinin octapeptide (CCK-8) applied either by superfusion (0.1-10 microM) or by pressure ejection elicited a slow depolarization in a portion of inferior mesenteric ganglion cells studied in vitro. The depolarization which persisted in a low Ca2+/high Mg2+ solution, or solution containing cholinergic antagonists, was often associated with a small to moderate increase in neuronal input resistance, and the response was reduced by conditioning hyperpolarization. Nicotinic excitatory postsynaptic potentials were consistently augmented during the course of CCK-8-induced depolarization. Our results, together with findings of the presence of CCK-immunoreactive fibers in the prevertebral ganglia, suggest that the peptide may serve to facilitate nicotinic transmission.

Animals↗

PubMed1986

Facilitation of nicotinic response in the guinea pig prevertebral neurons by substance P.

Fast excitatory postsynaptic potentials (f-EPSPs) evoked in guinea-pig inferior mesenteric ganglion cells were augmented during the course of non-cholinergic EPSP which is thought to be mediated by a substance P (SP)-like peptide. SP applied exogenously likewise increased the f-EPSPs and nicotinic depolarizations induced by acetylcholine applied by pressure ejection. Contrary to several earlier studies where SP was reported to interfere with nicotinic receptor activation, our results show that the peptide facilitates nicotinic transmission in the inferior mesenteric ganglia.

Animals↗

PubMed1986

Excitation of lateral horn neurons of the neonatal rat spinal cord by 5-hydroxytryptamine.

The effects of 5-hydroxytryptamine (5-HT) on lateral horn cells contained in thin in vitro slices of neonatal rat spinal cord were investigated by means of intracellular recording techniques. Superfusion of 5-HT (1-100 microM) to lateral horn cells caused a concentration-dependent membrane depolarization leading to, in some instances, repetitive cell discharges. A number of lateral horn cells could be activated antidromically by stimulating the ventral rootlets. The conduction velocity of the antidromic spikes was estimated to be 0.3-2 m/s which corresponds to that of the axons of rat sympathetic preganglionic neurons reported by others. The 5-HT depolarization evoked in neurons that could be activated antidromically was similar to that elicited from unidentified lateral horn cells. The depolarization induced by 5-HT could be partially eliminated by low Ca/high Mg solution or tetrodotoxin in a portion of lateral horn cells and was accompanied by an increase in membrane resistance. The response was nullified near the membrane potential at which the spike after hyperpolarization was abolished; a clear reversal of polarity was not observed at a more negative potential level. The 5-HT depolarization was reversibly blocked by methysergide and cyproheptadine and enhanced by fluoxetine, a 5-HT-uptake inhibitor. The results indicate that the indoleamine primarily exerted an excitatory action on lateral horn cells, including those tentatively identified as sympathetic preganglionic neurons, by a direct depolarization which appears to be mediated by decrease of a voltage-sensitive K conductance and partly by an indirect effect via the release of an excitatory substance(s).

Animals↗

PubMed1986

Tubocurarine suppresses slow calcium-dependent after-hyperpolarization in guinea-pig inferior mesenteric ganglion cells.

Intracellular recordings were made from neurones of the isolated guinea-pig inferior mesenteric ganglia. Single-spike potentials evoked by either depolarizing current pulses applied through the recording micro-electrode or stimulation of the hypogastric nerves were followed by an after-hyperpolarization (a.h.). The spike a.h. in 40% of the neurones, referred to herein as type I, had a relatively short duration (less than 50 ms) and exhibited a monophasic decay with a mean time constant (tau) of 11.4 ms. In the remaining cells (type II), the spike was followed by a long a.h. (greater than 100 ms) having a double-exponential decay; the fast and slow components of the a.h. are termed a.h.f and a.h.s, respectively, and they had mean tau values of 11.4 and 74 ms, respectively. A.h.f and a.h.s of type II neurones were reduced by membrane hyperpolarization and reversed their polarities between -80 and -90 mV. The reversal potentials shifted in a manner closely predicted by the Nernst equation as external K+ concentration was increased. Superfusion of low-Ca2+ high-Mg2+ solution to type II neurones reduced the a.h.f and a.h.s by 32 and 82%, respectively, indicating that a.h.s is largely Ca2+-dependent. Application of (+)-tubocurarine (10-100 microM) reversibly suppressed the a.h.s without affecting a.h.f in a concentration-dependent manner. Following a short train of action potentials evoked from type II neurones, the post-tetanic hyperpolarization (p.t.h.) was similarly depressed by (+)-tubocurarine in a dose-dependent manner. (+)-tubocurarine did not significantly change the amplitude of Ca2+-dependent spike potentials evoked in neurones bathed in Na+-free high-Ca2+ plus tetraethylammonium (5-10 mM) solution. The results indicate that (+)-tubocurarine selectively suppresses a.h.s, a slow Ca2+-dependent a.h., the consequence of which is a facilitation of repetitive discharges of the cells.

Action Potentials↗

PubMed1985

Vasopressin depolarizes lateral horn cells of the neonatal rat spinal cord in vitro.

The effects of vasopressin (VP) on lateral horn cells including a number of sympathetic preganglionic neurons contained in thin in vitro slices of neonatal rat spinal cord were investigated by means of intracellular recording techniques. Superfusion of (Arg8)-vasopressin (AVP, 0.01-1 microM) caused a depolarization leading, in the majority of lateral horn cells, to repetitive discharges. The AVP depolarization which could be partially reduced by low Ca/high Mg solution or tetrodotoxin, was accompanied by an increase in membrane resistance and the response was nullified near the membrane potential at which the spike afterhyperpolarization was abolished. A clear reversal of the response was not observed upon further hyperpolarization. The AVP response was blocked by the VP1 antagonist, D-(CH2)5 Tyr (Me)-AVP, whereas, deamino (D-Arg8-vasopressin), a VP2 agonist, at high concentrations (greater than or equal to 50 microM) was either ineffective or produced a small depolarization. The results indicate that AVP, acting mainly on VP1 receptors, excited lateral horn cells by a direct depolarization and an indirect effect via the release of an excitatory transmitter(s). A reduction of a voltage-dependent K conductance may underlie the depolarizing effect of AVP.

Animals↗

PubMed1985

Neurokinin A depolarizes neurons of the guinea pig inferior mesenteric ganglia.

Neurokinin A (NKA) applied either by superfusion (0.1-10 microM) or by pressure ejection evoked a slow membrane depolarization in neurons of the inferior mesenteric ganglia in vitro. The NKA-induced depolarization which was not significantly affected by reducing the Ca concentration or by tetrodotoxin was associated in most cases by a small-to-moderate increase in membrane resistance; however, conditioning hyperpolarization increased rather than decreased the response. The depolarization elicited by NKA was eliminated in the presence of substance P (SP) and the depolarization by SP in the presence of NKA. The results suggest that the actions of NKA on prevertebral neurons are similar to that of SP and that these two peptides may act on the same receptors or share similar ionic channels.

Animals↗

PubMed1985

Norepinephrine depolarizes lateral horn cells of neonatal rat spinal cord in vitro.

Superfusion of norepinephrine (NE) (1-50 microM) onto lateral horn cells, including antidromically identified sympathetic preganglionic neurons (SPNs), situated in thin transverse neonatal rat thoracolumbar spinal cord slices caused a membrane depolarization and repetitive cell discharges. The NE depolarization was associated with an increase in membrane resistance, and the response became smaller upon conditioning hyperpolarization; a clear reversal of polarity, however, was not observed. Pretreating the slices with phentolamine and prazosin but not yohimbine or propranolol prevented the depolarizing effect of NE. This finding, in conjunction with the evidence of the presence of noradrenergic fibers in the spinal cord, suggests that NE may serve as an excitatory neurotransmitter to neurons of the lateral horn.

Animals↗

PubMed1985

Prostaglandin E1 inhibits calcium-dependent potentials in mammalian sympathetic neurons.

Prostaglandin E1 (PGE1, 10-500 nM) reversibly depressed 3 types of calcium-dependent potentials associated with the spike potential of rabbit superior cervical ganglion cells, namely, the spike after-hyperpolarization, the post-tetanic hyperpolarization, and the Ca2+ spike evoked in a Na+-free/high Ca2+ solution. The results suggest that PGE1 reduces Ca conductance and that this action may underlie its inhibitory action on transmitter release at adrenergic and cholinergic nerve terminals.

Action Potentials↗

PubMed1985

Immunohistochemical and biochemical detection of serotonin in the guinea pig celiac-superior mesenteric plexus.

Serotonin (5-HT) in the guinea pig celiac-superior mesenteric plexus was quantitatively measured by HPLC and visualized by an immunohistochemical method. Preincubation of the ganglia in a Krebs solution containing L-tryptophan and pargyline markedly elevated the content of 5-HT and K+ solution caused a release of 5-HT into the incubation medium. 5-HT immunoreactivity was localized to dense but unevenly distributed nerve fibers throughout the plexus and to small diameter cells commonly referred to as small intensely fluorescent cells. These findings provide evidence of an extensive network of 5-HT-containing neural elements in the guinea pig prevertebral ganglia.

Animals↗

PubMed1985

Facilitation and inhibition of nicotinic transmission by eserine in the sympathetic ganglia of the rabbit.

The effects of eserine on neurons and on ganglionic transmission of the isolated superior cervical ganglia of the rabbit were investigated by means of intracellular recording techniques. At the concentration of 10 microM or less, eserine reversibly increased the amplitude and duration of the fast excitatory postsynaptic potential (f-epsp) induced by preganglionic nerve stimulation and of the membrane depolarization evoked by iontophoretically-applied acetylcholine (ACh), but not carbachol. At the concentration of 50 microM or more, eserine consistently and reversibly depressed the fast excitatory postsynaptic potential as well as the depolarization induced by iontophoretic application of either ACh or carbachol. Furthermore, depolarization by ACh evoked in a low Ca/high Mg solution, which blocked the liberation of transmitter was similarly reduced by eserine in greater concentrations. The passive membrane properties of the sympathetic neurons were not significantly altered by eserine in the majority of neurons studied. The results indicate that the facilitatory action of eserine on ganglionic transmission may be explained by its anticholinesterase activity, whereas eserine-induced block of transmission appears to be related to a direct interaction between the compound and the postsynaptic ACh receptor-channel complex.

Acetylcholine↗

PubMed1985

Synaptic transmission in the rabbit inferior mesenteric ganglion.

Electrical properties, cholinergic neurotransmission and non-cholinergic neurotransmission in the rabbit inferior mesenteric ganglion (IMG) in vitro were examined with intracellular recording techniques. A single ganglionic neuron received an average of 42 nicotinic cholinergic synaptic inputs. An atropine-sensitive slow excitatory postsynaptic potential not followed by a non-cholinergic late slow excitatory postsynaptic potential (LS-EPSP) was observed in 7% of the cells. In 63% of the cells a LS-EPSP insensitive to antagonism of nicotinic and muscarinic receptors was observed following repetitive nerve stimulation. The involvement of substance P (SP) in the genesis of the LS-EPSP was tested by applications of SP, applications of SP antagonists and applications of capsaicin. Neither SP, SP antagonists nor capsaicin affected the LS-EPSP. These findings distinguish the LS-EPSP in the rabbit IMG from its counterpart in the guinea pig IMG where SP has been proposed as the mediator of the LS-EPSP. A late slow inhibitory postsynaptic potential was observed in 13% of the cells. This hyperpolarization followed repetitive nerve stimulation and was insensitive to blockade of cholinergic receptors. There is a marked convergence of subthreshold fast excitatory postsynaptic potentials (F-EPSPs) of both central and peripheral origin onto these cells. The LS-EPSP could provide a mechanism for increasing the likelihood of temporal and/or spatial summation of these fast synaptic inputs, thereby increasing the probability of action potential generation in the ganglion cells.

Action Potentials↗

PubMed1984

Vasoactive intestinal polypeptide facilitates muscarinic transmission in mammalian sympathetic ganglia.

Vasoactive intestinal polypeptide (VIP) in the concentration of 1 microM or less markedly and selectively increased the amplitude and duration of the muscarinic slow excitatory postsynaptic potential (EPSP) without appreciably affecting the nicotinic fast EPSP or the non-cholinergic EPSP of guinea pig inferior mesenteric ganglion cells. The membrane depolarization evoked by the muscarinic agonist, acetyl-beta-methylcholine in these neurons was similarly enhanced by VIP. Our results suggest that the peptide may be a neuromodulator effective in enhancing the sensitivity of postsynaptic muscarinic receptors to acetylcholine in the vertebrate sympathetic ganglia.

Acetylcholine↗

PubMed1984

Actions of 4-aminopyridine on mammalian ganglion cells.

The effects of 4-aminopyridine (4-AP) on membrane electrical properties and synaptic transmission in neurons of the isolated rabbit superior cervical ganglion were investigated. 4-AP (0.03-0.1 mM) increased the amplitude of the fast excitatory postsynaptic potential (f-EPSP) without affecting appreciably either the acetylcholine (ACh) depolarization induced by iontophoresis of ACh or the passive and active membrane properties of the neurons. At concentrations of 1-5 mM, 4-AP reversibly depressed the amplitude of the f-EPSP as well as the ACh depolarization; a slight to moderate prolongation of the action potential duration was observed. In addition to the effects on evoked synaptic potentials, 4-AP induced spontaneous discharges which were abolished reversibly by curare, low Ca solution or Co. The results indicate that 4-AP at low concentrations facilitated evoked as well as spontaneous release of ACh by a presynaptic mechanism, whereas at higher concentrations it exerted a curare-like effect on the postsynaptic membrane.

4-Aminopyridine↗