Agonists that suppress M-current elicit phosphoinositide turnover and Ca2+ transients, but these events do not explain M-current suppression.
The hypothesis that acetylcholine, substance P, and LHRH suppress M-current by activating phospholipase C was tested. Each agonist caused turnover of phosphoinositide, as measured by release of inositol phosphates, and a modest transient rise in intracellular free Ca2+ ([ Ca2+]i), as determined with fura-2. Active phorbol esters depressed M-current only 50% and did not prevent further suppression by LHRH. M-current, its control by agonists, and its depression by phorbol esters were not affected by adding inositol trisphosphate or Ca2+ buffers with high or low Ca2+ to the whole-cell, voltage-clamp pipette. We conclude that phospholipase C activation does occur but does not mediate the suppression of M-current by agonists. Caffeine produced large [Ca2+]i transients and acted as an agonist to suppress M-current.
Pfaffinger
P J
PJ
Department of Physiology and Biophysics, University of Washington School of Medicine, Seattle 98195.
Leibowitz
M D
MD
Subers
E M
EM
Nathanson
N M
NM
Almers
W
W
Hille
B
B
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001572:Benzofurans; D002118:Calcium / Q000378:metabolism*; D004553:Electric Conductivity; D004789:Enzyme Activation; D005456:Fluorescent Dyes; D016257:Fura-2; D005728:Ganglia, Sympathetic / Q000187:drug effects / Q000502:physiology*; D007987:Gonadotropin-Releasing Hormone / Q000494:pharmacology*; D066298:In Vitro Techniques; D007295:Inositol Phosphates / Q000378:metabolism*; D009116:Muscarine / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D010716:Phosphatidylinositols / Q000378:metabolism*; D011898:Ranidae; D013373:Substance P / Q000494:pharmacology*; D010738:Type C Phospholipases / Q000378:metabolism
D001572:Benzofurans; D005456:Fluorescent Dyes; D007295:Inositol Phosphates; D010716:Phosphatidylinositols; D013373:Substance P; D007987:Gonadotropin-Releasing Hormone; D001285:Atropine; D009116:Muscarine; D010738:Type C Phospholipases; D000109:Acetylcholine; D002118:Calcium; D016257:Fura-2