Ganglionic Neurotransmission

Quit Smoking Magic

Quit Smoking Cigarette

Get Instant Access

Neurotransmission in autonomic ganglia is a more complex process than that described by a single neurotransmitter-receptor system, with at least 4 distinct changes in membrane potential elicited by stimulation of the preganglionic nerve. The primary event involves a rapid depolarization of postsynaptic sites by ACh. An action potential is generated in the postganglionic neuron when the initial EPSP attains sufficient amplitude; in mammalian sympathetic ganglia in vivo, effective transmission likely requires activation at multiple synapses. The EPSP is followed by a slow inhibitory postsynaptic potential (IPSP), a slow EPSP, and a late, slow EPSP; slow IPSP and slow EPSP are not seen in all ganglia. The initial EPSP is mediated through nicotinic (N) receptors, the slow IPSP and EPSP through M2 and M1 muscarinic receptors, and the late, slow EPSP through various peptidergic receptors in response to peptides released from presynaptic nerve endings or interneurons in specific ganglia (see Chapter 7). The slow EPSPs result from decreased K+ conductance (the M current, which regulates the sensitivity of the cell to repetitive fast-depolarizing events). The IPSP is unaffected by nicotinic receptor antagonists but is generally sensitive to blockade by both atropine and a adrenergic receptor antagonists; apparently, ACh released at the pre-ganglionic terminal acts on catecholamine-containing interneurons to stimulate the release of dopamine (DA) or norepinephrine (NE); the catecholamine, in turn, produces hyperpolarization (an IPSP) of ganglion cells. Small, intensely fluorescent (SIF) cells containing DA and NE and adrenergic nerve terminals are present in ganglia and presumably participate in IPSP generation (see Figure 9-5 in the 11th edition of the parent text).

The relative importance of secondary pathways and the identity of modulating transmitters differ amongst individual ganglia and between parasympathetic and sympathetic ganglia. Myriad pep-tides (gonadotropin-releasing hormone, substance P, angiotensin, calcitonin gene-related peptide [CGRP], vasoactive intestinal polypeptide, neuropeptide Y, and enkephalins), are present in ganglia and are presumed to mediate the late slow EPSP. Other neurotransmitters, such as 5-HT and GABA, are known to modify ganglionic transmission. Precise details of their modulatory actions are not understood; they are most closely associated with the late slow EPSP and inhibition of the M current. Secondary transmitters (and their antagonists) only modulate the initial EPSP. By contrast, conventional ganglionic blocking agents can inhibit ganglionic transmission completely.

Drugs that stimulate cholinergic receptor sites on autonomic ganglia can be grouped into two categories. The first group consists of drugs with nicotinic specificity, including nicotine itself. Their excitatory effects on ganglia are rapid in onset, are blocked by ganglionic nicotinic receptor antagonists, and mimic the initial EPSP. The second group is composed of agents such as muscarine, McN-A-343, and methacholine. Their excitatory effects on ganglia are delayed in onset, blocked by atropine-like drugs, and mimic the slow EPSP.

Ganglionic blocking agents acting on the nicotinic receptor may be classified into two groups. The first group includes drugs that initially stimulate the ganglia by an ACh-like action and then block them because of a persistent depolarization (e.g., nicotine); prolonged application of nicotine results in desensitization of the cholinergic receptor site and continued blockade. Drugs in the second group of blockers, of which hexamethonium and trimethaphan are prototypes, impair transmission either by competing with ACh for ganglionic nicotinic receptor sites (trimethaphan) or by blocking the channel after it opens (hexamethonium). Regardless of the mechanism, the initial EPSP is blocked, and ganglionic transmission is inhibited.

Was this article helpful?

0 0
Beating The Butt On Your Own

Beating The Butt On Your Own

Need To Stop Smoking? Are You Willing To Follow My Powerful Strategies To Stop Smoking And Vividly Transform Your Life Today? Proven Tips, Tools and Tactics To Stop Smoking And Live An Awesome Life You Always Wanted.

Get My Free Ebook

Post a comment