Phosphatidylinositol hydrolysis is involved in production of Ca(2+)-dependent currents, but not non-selective cation currents, by muscarine in chromaffin cells.
Whether phosphatidylinositol hydrolysis and a subsequent Ca2+ mobilization are responsible for muscarine-induced transient outward currents (IO) and non-selective cation currents (INS) in the guinea-pig chromaffin cell was investigated using the perforated patch method. IO, but not INS, failed to be reproduced in Ca(2+)-free solution and was markedly reduced by prior exposure to caffeine under Ca(2+)-free conditions or by addition to normal solution of cyclopiazonic acid (CPA), a Ca2+ ATPase inhibitor. Application of CPA in Ca(2+)-free solution, however, suppressed INS by about 50% in 73% of the cells tested. Bath application of 1.5 mM neomycin, a phospholipase C inhibitor, induced the time-dependent decline of IO with near abolition at 20 min or less, whereas it produced a time-independent decrease of INS and an inwardly rectifying K+ current. INS in the presence or absence of neomycin was well fitted to rectangular hyperbolas with the same ED50 of 2.17 microM, but with a 33% smaller maximum amplitude in the former, indicating a non-competitive inhibition by neomycin. We conclude that, while phosphatidylinositol hydrolysis mediates the production of IO, it does not mediate that of INS by muscarine.
Inoue
M
M
Department of Physiology, School of Medicine, Fukuoka University, Japan.
Sakamoto
Y
Y
Imanaga
I
I
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002837:Chromaffin Granules / Q000187:drug effects / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006168:Guinea Pigs; D006868:Hydrolysis; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology*; D009116:Muscarine / Q000494:pharmacology*; D009355:Neomycin / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000378:metabolism*
D007211:Indoles; D007473:Ion Channels; D010716:Phosphatidylinositols; D009116:Muscarine; D009355:Neomycin; D002118:Calcium; C000543:cyclopiazonic acid