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Cyclic AMP‐Independent Inhibition of Voltage‐Sensitive Calcium Channels by Forskolin in PC12 Cells
Author(s) -
Park TaeJu,
Kim KyongTai
Publication year - 1996
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.1471-4159.1996.66010083.x
Subject(s) - forskolin , adenylyl cyclase , medicine , endocrinology , adcy10 , adcy9 , cyclase , chemistry , biology , stimulation
Forskolin has been used to stimulate adenylyl cyclase. However, we found that forskolin inhibited voltage‐sensitive Ca 2+ channels (VSCCs) in a cyclic AMP (cAMP)‐independent manner in PC12 cells. Ca 2+ influx induced by membrane depolarization with 70 m M K + was inhibited when cells were preincubated with 10 µ M forskolin. Almost maximum inhibitory effect on Ca 2+ influx without any significant increase in cellular cAMP level was observed in PC12 cells exposed to forskolin for 1 min. In addition, the forskolin effect on Ca 2+ influx was not affected by the presence of 2′,5′‐dideoxyadenosine, an inhibitor of adenylyl cyclase that reduces dramatically forskolin‐induced cAMP production. 1,9‐Dideoxyforskolin, an inactive analogue of forskolin, also inhibited ∼80% of Ca 2+ influx induced by 70 m M K + without any increase in cAMP. The data suggest that forskolin and its analogue inhibit VSCCs in PC12 cells and that the inhibition is independent of cAMP generation.