摘要:

Over the last 20 years there has been a marked increase in the understanding of the biophysical properties of neurones in autonomic ganglia. During the same time period, there have been advances in immunohistochemistry which have shown that the autonomic ganglia are rich sources of a variety of neuroactive peptides and monoamines. Although physiological studies have underlined the role of enteric and prevertebral ganglia in the control of peristalsis and micturition, very little is known about the physiological role of many of the other autonomic ganglia.The objective of the International Brain Research Organization satellite symposium held in Edmonton, Alberta, during August 1991, was to bring together the biophysicists, morphologists, physiologists, and pharmacologists to evaluate the current status of our understanding of the autonomic ganglia. Posters and four sessions of invited talks were presented over a three-day period. The papers that appear in this issue detail the content of some of these talks.The organizers gratefully acknowledge the financial support provided by the Alberta Heritage Foundation for Medical Research, the Medical Research Council of Canada, Astra Pharma Inc., the University of Alberta Conference Fund, Nordic Laboratories, Merck Frosst Canada, Axon Instruments, Novopharm Ltd., Bio-Méga Inc., Chembiomed, Newport Instruments, the City of Edmonton, Charles River Canada, and Mandel Scientific.

ISSN:0008-4212    

DOI:10.1139/y92-236

出版商:NRC Research Press    

年代:1992

数据来源: NRC

摘要:

The existence of two muscarinically mediated slow postsynaptic potentials (PSPs) and a noncholinergic (peptidergic) late-slow PSP was established in the 1960s. These have synaptic delays and PSP durations 100–10 000 times those for the nicotinic (fast) excitatory post-synaptic potential (EPSP). Evidence is reviewed for and against the proposal that, in rabbit superior cervical ganglia, the slow (s-) inhibitory postsynaptic potential requires a second transmitter, dopamine, released by muscarinic action on interneurones (the small, intensely fluorescent cells). The s-EPSP in frog ganglia appears only in already depolarized cells by a muscarinic closure of the M (voltage-sensitive K+) channels. But the large s-EPSP in mammalian neurones, not depolarized, is generated largely via other mechanisms, especially one involving cyclic GMP. Dopamine also produces a long-term enhancement (LTE) of the muscarinic slow PSPs in rabbit superior cervical ganglia, whether dopamine is applied exogeneously or released intraganglionically by preganglionic nerve impulses at 10 s−1. LTE is producible heterosynaptically, and it persists well over 3 h; a noncholinergic (peptide?) transmitter may contribute to the initial 30 min of LTE. LTE is mediated by a D1receptor coupled to cyclic AMP; it is blocked by cyclic GMP or low Ca2+or calmidazolium (a calmodulin inhibitor). The modulatory process of LTE has certain similarities to, but also fundamental differences from, the long-term potentiation known in the hippocampus.Key words: muscarinic synapses, peptidergic synapses, dopamine actions, neuromodulation, postsynaptic long-term enhancement.

ISSN:0008-4212    

DOI:10.1139/y92-237

出版商:NRC Research Press    

年代:1992

数据来源: NRC

摘要:

Slow excitatory postsynaptic potentials in sympathetic ganglia often involve suppression of a voltage-dependent potassium current termed the M current. This current is suppressed by the muscarinic action of acetylcholine, by peptides such as luteinizing hormone releasing hormone, and sometimes by α-adrenoceptor agonists. Activation of β-adrenoceptors sometimes produces weak potentiation. The voltage dependence of the M current is such that its suppression increases the excitability of ganglionic neurones. Since this sometimes leads to spontaneous discharge, activation of the slow excitatory postsynaptic potential mechanism (or modulation of M current) within a sympathetic ganglion produces effects that manifest in the autonomic outflow to the target organ. In frogs, M currents are present in the neurones of both paravertebral sympathetic ganglia and cardiac parasympathetic ganglia. Since the M current is suppressed by adrenaline in the parasympathetic ganglia and these ganglia often receive adrenergic fibres from sympathetic ganglia, this might reflect an important means of interaction between the two branches of the autonomic system. At the cellular level, M-current suppression is little affected by drugs that interfere with membrane phosphorylation–dephosphorylation processes. This observation is discussed in relationship to the current understanding of the transduction mechanism for agonist-induced M-current suppression.Key words: autonomic nerve, K+channel, G protein, muscarinic mechanism, adrenergic mechanism.

ISSN:0008-4212    

DOI:10.1139/y92-238

出版商:NRC Research Press    

年代:1992

数据来源: NRC

摘要:

Understanding the integrative significance of synaptic cotransmission is a central problem in autonomic physiology. What are the functional roles of slow synaptic potentials in autonomic ganglia? This paper reviews the problem and its historical roots by focusing on work in the amphibian paravertebral sympathetic system. The phenotypic properties that distinguish the sympathetic B and C cell systems are summarized. Then, a synaptic gain hypothesis is proposed for the integrative function of muscarinic and peptidergic synapses in the vasomotor C system. The model states that the peripheral output of the vasomotor system is subject to synaptic amplification by two gain stages in series. The first gain stage is postulated to arise in ganglia from interactions between two slow postsynaptic potentials; the excitatory response mediated by luteinizing hormone releasing hormone, and the inhibitory response mediated by the muscarinic action of acetylcholine. The second gain stage is postulated to arise in arteries from interactions between two postganglionic cotransmitters: epinephrine and neuropeptide Y. A circuit with these properties would enable preganglionic patterns of electrical activity to regulate the system's output over a wider dynamic range than possible without cotransmitters.Key words: vasomotor sympathetic neurons, muscarinic synapses, luteinizing hormone releasing hormone, neuropeptide Y, neuronal model.

ISSN:0008-4212    

DOI:10.1139/y92-239

出版商:NRC Research Press    

年代:1992

数据来源: NRC

摘要:

A stimulus train to preganglionic axons produces long-term potentiation (LTP) of population responses of sympathetic ganglion cells evoked by the same or by other converging axons. The present study shows that preganglionic axons emerging from the spinal cord in different thoracic rami, and converging onto a common pool of ganglion cells that innervate a single target, differ in their ability to induce LTP. In anesthetized cats under partial nicotinic block with hexamethonium, the nictitating-membrane (NM) contraction evoked by stimulation of the first (T1) and third (T3) thoracic white rami (WR) was recorded. Each ramus produced a contraction of similar amplitude. In contrast, the homosynaptic potentiation produced by a 40-Hz 10-s train differed markedly. T1WR produced a potentiation of duration comparable to that produced by stimulation of the cervical sympathetic trunk, while T3WR produced either no potentiation or a potentiation of much shorter duration. The NM response evoked by T3WR, however, was potentiated by similar extent and duration as was the response evoked by T1WR when the train was applied to T1WR (heterosynaptic LTP). This suggests that the ganglionic synapses made by T3WR possess the mechanism for expressing LTP. Conversely, T3WR was ineffective at potentiating heterosynaptically the NM response evoked by T1WR. These results suggest that the ability to produce or release the LTP inducer varies markedly among sympathetic preganglionic neurons.Key words: preganglionic neuron heterogeneity, long-term potentiation induction, synaptic transmission, neuropeptides.

ISSN:0008-4212    

DOI:10.1139/y92-240

出版商:NRC Research Press    

年代:1992

数据来源: NRC

摘要:

Correlated histochemical, immunocytochemical, and electrophysiological experiments have been undertaken to identify putative neurotransmitter–neuromodulator substances in cells and fibers in the parasympathetic cardiac ganglion of the mudpuppy,Necturus maculosus, and to determine the action of these agents on the properties of the parasympathetic postganglionic neurons. The mudpuppy cardiac ganglion contains two neuron types: large parasympathetic postganglionic neurons and smaller intrinsic neurons initially identified as small intensely fluorescent cells. We have shown that the postganglionic neurons contain both acetylcholine and a galanin-like neuropeptide. Also, we have demonstrated that the intrinsic neurons contain a number of different biogenic amines such as dopamine and serotonin, as well as neuropeptides including a substance P-like peptide and a galanin-like peptide. The results of these studies indicate that the anatomical and histochemical organization of the mudpuppy cardiac ganglion is more complex than that seen in other amphibians and is very similar to that found in most mammalian species. Previously, we showed that galanin has actions that make it of interest as a potential inhibitory neurotransmitter in the mudpuppy cardiac ganglion. Galanin hyperpolarizes and decreases membrane excitability in most parasympathetic neurons. Here we show that galanin initiates membrane hyperpolarization by activating a voltage- and time-dependent potassium conductance. We also present the initial results of ongoing studies which indicate that calcitonin gene-related peptide can depolarize some of the parasympathetic neurons as well as evidence that serotonin initiates depolarization in many parasympathetic neurons. This serotonin-induced depolarization consists of an initial transient depolarization followed by a longer, more slowly developing depolarization. Action potential activity is stimulated during the initial period of depolarization, but depressed during the later, slow depolarization. The results of these electrophysiological experiments suggest that many of the bioactive substances that have been identified in the different cells and nerve fibers within the cardiac ganglion affect the excitability of the postganglionic neurons. In conclusion, we suggest that the results of the studies summarized in this review demonstrate that the cardiac ganglion in the mudpuppy is not simply a relay station. Rather, the cardiac ganglion has a complex organization and exhibits a diversity of physiological responses, indicating that it very likely is another site of integration for control of cardiac function.Key words: parasympathetic neurons, cardiac ganglion, neuropeptides, biogenic amines, galanin, serotonin.

ISSN:0008-4212    

DOI:10.1139/y92-241

出版商:NRC Research Press    

年代:1992

数据来源: NRC

摘要:

Electrical activities of the postganglionic neurons in the superior cervical ganglia of rabbits are modulated in various ways following activation of the subtypes of muscarinic acetylcholine receptors, (i) M1receptors mediate a slow depolarization consisting of at least three types of ionic conductance changes, and one of these is possibly mediated by cyclic GMP. (ii) M2receptors mediate a slow hyperpolarization that seems to be generated by inositol triphosphate derived from phosphatidylinositol breakdown. (iii) M2receptors also cause, through an activation of C kinase, a suppression of Ca entry during action potentials that results in a characteristic change in the action potentials and thereby modulates excitability of superior cervical ganglion neurons. Each subtype of muscarinic receptors thus regulates different pathways of intracellular transduction and modulates the electrical signaling of sympathetic neurons.Key words: superior cervical ganglion, electrical signals, muscarinic responses, muscarinic receptor subtypes, second messengers.

ISSN:0008-4212    

DOI:10.1139/y92-242

出版商:NRC Research Press    

年代:1992

数据来源: NRC

摘要:

Much evidence has accumulated suggesting that neurons in autonomic and dorsal root ganglia possess voltage-dependent currents that link with transmitter receptors through intracellular signal transduction systems. The M current (IM), a voltage-dependent potassium current, was activated at potentials more positive than −65 mV, while the H current (IH), a voltage-dependent nonselective cationic current, was activated at potentials more negative than −50 mV. The hydrolyzable form of ATP was required to activateIMandIH. Intracellular application of calmodulin enhanced the amplitude ofIMin a calcium-dependent manner.IMwas reduced by W-7, a calmodulin antagonist, and by ML-9, an inhibitor of calmodulin-dependent protein kinase.IHwas enhanced by intracellular loading with cyclic adenosine monophosphate (AMP) or bath application of forskolin and membrane-permeable cyclic AMP analogues. Isobutylmethylxanthine also increased the maximal conductance ofIH.IHwas depressed by H-8 but not by phorbol ester. It is concluded that the resting membrane conductance of these ganglion cells can be regulated by basal activities of calmodulin-dependent protein kinase and A kinase.Key words: peripheral neurons, M current, H current, calmodulin, adenylate cyclase.

ISSN:0008-4212    

DOI:10.1139/y92-243

出版商:NRC Research Press    

年代:1992

数据来源: NRC

摘要:

The calcium current of frog sympathetic neurons has relatively rapid activation kinetics (τ < 3 ms) in response to changes in voltage. Pharmacologically, the current is blocked ~90% by ω-conotoxin, but < 10% by dihydropyridine antagonists. This suggests that nearly all of the current is N type. However, inactivation is slow and incomplete even for depolarizations lasting > 1 s, consistent with recent evidence that N-type channels do not always inactivate rapidly. The calcium current is partially inhibited via receptors for acetylcholine, luteinizing hormone releasing hormone, substance P, ATP, and norepinephrine. These effects are mimicked by internal dialysis with GTP-γ-S, suggesting involvement of a G protein. The transmitters affect the activation kinetics of the calcium current in a voltage-dependent manner, which can be modeled as a reversible shift of some channels to "reluctant" states in which strong depolarization is needed to produce channel opening. The effects of transmitters develop and recover witht½~ 1–2 s, so if a second messenger is involved in receptor – calcium channel coupling, it must act rapidly.Key words: norepinephrine, ω-conotoxin, dihydropyridine, inactivation, G protein.

ISSN:0008-4212    

DOI:10.1139/y92-244

出版商:NRC Research Press    

年代:1992

数据来源: NRC

摘要:

Spatial and temporal changes in the intracellular free Ca2+concentration in response to Ca2+influx at the cell membrane and to Ca2+release from intracellular organelles were studied by recording fluorescence of Ca2+-sensitive probes, fura 2 or indo 1, with conventional epifluorescence or confocal laser-scanning microscopy combined with recordings of Ca2+-dependent membrane responses in bullfrog sympathetic ganglion cells. It was found that an increase in the intracellular Ca2+induced by (an) action potential(s) in freshly isolated ganglion cells bathed in Ringer's solution was solely a result of Ca2+influx, while a rise in the intracellular Ca2+by Ca2+current in voltage-clamped cultured neurones was caused by not only Ca2+influx but also Ca2+release. This Ca2+release was suggested to occur by a voltage-dependent (and graded) mode of activation of a Ca2+-induced Ca2+release mechanism, explaining the lack of Ca2+release by action potentials (because of their short-lasting depolarization) in freshly isolated neurones. In both cases, there was an inward spread of an increase in intracellular Ca2+. On the other hand, all or nothing activation of Ca2+-induced Ca2+release occurred in the presence of caffeine, leading to the oscillation of Ca2+in the cells. Characteristics of this mode of Ca2+release and unique properties of drugs to block Ca2+release were described. Finally, the physiological significance of different types of Ca2+release was discussed.Key words: Ca2+current, Ca2+-induced Ca2+release, Ca2+transient, confocal microscope, bullfrog sympathetic ganglion cells.

ISSN:0008-4212    

DOI:10.1139/y92-245

出版商:NRC Research Press    

年代:1992

数据来源: NRC