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Regulation of the L‐Type Ca 2+ Channel Current in Rat Pinealocytes
Author(s) -
Chik Constance L.,
Li Bing,
Karpinski Edward,
Ho Anthony K.
Publication year - 1999
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1999.0720073.x
Subject(s) - okadaic acid , calphostin c , phosphatase , protein kinase a , biology , protein kinase c , protein kinase inhibitor , kinase , calphostin , pinealocyte , staurosporine , microbiology and biotechnology , phosphoprotein , biochemistry , chemistry , phosphorylation , endocrinology , pineal gland , melatonin
Abstract : In the present study, the role of phosphoproteinphosphatase in the regulation of L‐type Ca 2+ channel currents inrat pinealocytes was investigated using the whole‐cell version of thepatch‐clamp technique. The effects of three phosphatase inhibitors, calyculinA, tautomycin, and okadaic acid, were compared. Although all three inhibitorswere effective in inhibiting the L‐type Ca 2+ channel current,calyculin A was more potent than either tautomycin or okadaic acid, suggestingthe involvement of phosphoprotein phosphatase‐1. To determine the kinaseinvolved in the regulation of these channels, cells were pretreated with H7 (anonspecific kinase inhibitor), H89 (a specific inhibitor of cyclicAMP‐dependent kinase), KT5823 (a specific inhibitor of cyclic GMP‐dependentkinase), or calphostin C (a specific inhibitor of protein kinase C).Pretreatment with either H7 or calphostin C decreased the inhibitory effect ofcalyculin A on the L‐type Ca 2+ channel current. In contrast,pretreatment with H89 or KT5823 had no effect on the inhibition caused bycalyculin A. Based on these observations, we conclude that basal phosphataseactivity, probably phosphoprotein phosphatase‐1, plays an important role inthe regulation of L‐type Ca 2+ channel currents in rat pinealocytes by counteracting protein kinase C‐mediated phosphorylation.