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Science 17 June 1988:
Vol. 240. no. 4859, pp. 1652 - 1655
DOI: 10.1126/science.2454506
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Articles

Science, Vol 240, Issue 4859, 1652-1655
Copyright © 1988 by American Association for the Advancement of Science

articles

Effect of forskolin on voltage-gated K+ channels is independent of adenylate cyclase activation

T Hoshi, SS Garber, and RW Aldrich

Department of Neurobiology, Stanford University, School of Medicine, CA 94305.

Forskolin is commonly used to stimulate adenylate cyclase in the study of modulation of ion channels and other proteins by adenosine 3',5'-monophosphate (cAMP)-dependent second messenger systems. In addition to its action on adenylate cyclase, forskolin directly alters the gating of a single class of voltage-dependent potassium channels from a clonal pheochromocytoma (PC12) cell line. This alteration occurred in isolated cell-free patches independent of soluble cytoplasmic enzymes. The effect of forskolin was distinct from those of other agents that raise intracellular cAMP levels. The 1,9-dideoxy derivative of forskolin, which is unable to activate the cyclase, was also effective in altering the potassium channel activity. This direct action of forskolin can lead to misinterpretation of results in experiments in which forskolin is assumed to selectively activate adenylate cyclase.


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