"Upstream" regulation of the release probability in sympathetic nerve varicosities.
The results appear to support the following tentative working hypothesis. (1) Nerve impulse-induced transmitter release from sympathetic nerve varicosities is monoquantal and highly intermittent (probability range: 0-0.03). (2) Nerve impulses invade varicosities as all-or-none, Na+ channel-dependent action potentials; invasion failure may be rare. (3) The release probability is not controlled by properties (amplitude or duration) of the invading action potential or the resulting Ca2+ current, but by the availability of an as yet unidentified permissive factor. (4) The permissive factor is actively transported intra-axonally, probably in association with organelles (LDVs?). (5) The activation and/or transport of the permissive factor are controlled "upstream" of the varicosity; they depend on Ca2+ influx through channels insensitive to nifedipine (hence, not of L-type) but blocked by Cd2+ and apparently opened by slight depolarization of the resting membrane, in this respect behaving more as T- than N-type channels. (6) A high resting K+ efflux "upstream" of the varicosity restricts the availability of the permissive factor; it is the main mechanism maintaining the (economically necessary) low release probability. (7) Prejunctional agonists do not inhibit transmitter secretion by causing a conduction block or by reducing the action potential-induced Ca2+ influx into the varicosity itself, but by depressing the Ca2(+)-dependent activation and/or transport of the permissive factor; they act at least in part via receptors "upstream" of the varicosity. (8) This hypothesis for regulation of the release probability in sympathetic nerves may apply, at least in part, to other neurons as well.
Stjärne
L
L
Department of Physiology, Karolinska Institutet, Stockholm, Sweden.
Msghina
M
M
Stjärne
E
E
D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000502:physiology; D008959:Models, Neurological; D009411:Nerve Endings / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000378:metabolism*; D011188:Potassium / Q000037:antagonists & inhibitors; D015221:Potassium Channels / Q000187:drug effects; D011336:Probability; D013564:Sympathetic Nervous System / Q000502:physiology*
D018377:Neurotransmitter Agents; D015221:Potassium Channels; D011188:Potassium; D002118:Calcium