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PMID: 6325010 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Kinetics of acetylcholine-activated cation channel blockade by the calcium antagonist D-600 in Aplysia neurons.

Cellular and molecular neurobiology ·Vol. 3 ·No. 4 ·1983-12-00 ·Pages 329-44

Slater NT, Haas HL, Carpenter DO

Abstract

The effects of the calcium channel blocker D-600 on the cation channels activated by acetylcholine (ACh) was studied in voltage-clamped Aplysia neurons by voltage-jump relaxation analysis. D-600 blocked the steady-state ACh current in a highly voltage-dependent manner, the degree of antagonism increasing with membrane hyperpolarization. In the presence of D-600 the current relaxations following hyperpolarizing command steps became biphasic. The time constants of ACh-induced current relaxations (tau f), which approximate the mean channel lifetime, were reduced in a voltage-dependent manner, the degree of reduction of tau f increasing with increasing membrane potential. In addition to the acceleration of tau f, a slow, inverse kinetic component (tau s) of the relaxation appeared in the presence of D-600. The rate of this inverse kinetic component was accelerated either by increasing the agonist or antagonist dose or by increasing the membrane potential. These results suggest that D-600 acts to antagonize the acetylcholine response through a blockade of the open state of the transmitter-activated cation channel. Possible kinetic schemes for this interaction are discussed.

MeSH Terms
Acetylcholine/pharmacology Animals Aplysia Calcium/metabolism Dose-Response Relationship, Drug Gallopamil/pharmacology Ganglia/drug effects Ion Channels/drug effects Kinetics Membrane Potentials/drug effects Neurons/drug effects Receptors, Cholinergic/drug effects Synaptic Transmission/drug effects Verapamil/pharmacology
Chemicals
Ion Channels Receptors, Cholinergic Gallopamil Verapamil Acetylcholine Calcium
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Slater N T
Haas H L
Carpenter D O
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41 references, click to expand
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Article Info
Journal
Cellular and molecular neurobiology
Abbr.
Cell Mol Neurobiol
ISSN
0272-4340
DOI
10.1007/BF00734714
Published
1983-12-00
Pages
329-44
Language
English
Region
United States
NLM ID
8200709
Subset
IM
Grants
NINDS NIH HHS · NS18435 · United States
External Links
PubMed source DOI: 10.1007/BF00734714 View journal details
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