Effect of ?-conotoxin GVIA on Ca(2+) influx and endogenous acetylcholine release from chicken brain preparations.
?-Conotoxin GVIA (?-conotoxin) is an inhibitor of neuronal voltage sensitive calcium channels (VSCCs). We have examined the effects of various manipulations aimed at elucidating the effects of ?-conotoxin particularly on K(+) stimulated (45)Ca(2+) influx and endogenous acetylcholine (ACh) release. The initial phase of K(+) stimulated (45)Ca(2+) influx was accompanied by a large rapid release of ACh measured by a modification of the chemiluminescent technique of Israël and Lesbats (J. Neurochem.39, 248-250, 1982). ACh release was greatly reduced (?90% ) in Ca(2+) free solution or by Cd(2+) (100 ?M) period ?-conotoxin (1 ?M) completely blocked the initial phase of (45)Ca(2+) influx (1-3 s) from synaptosomes and reduced K(+) stimulated ACh release from tissue slices. ?-Conotoxin (0.1 ?M) reduced ACh release which was reversed in the presence of high Ca(2+) concentrations. The dihydropyridine VSCC inhibitor (?)202-791 or agonist (+)202-791 had no effect on ACh release or (45)Ca(2+) influx. The pattern of responses on (45)Ca(2+) influx and endogenous ACh release was consistent with the suggestion that ?-conotoxin inhibits N-type VSCCs and that these channels are intimately related to ACh release.
Lundy
P M
PM
Biomedical Defence Section, Defence Research Establishment Suffield, Ralston, Alberta, Canada T0J 2N0.
Stauderman
K
K
Goulet
J C
JC
Frew
R
R