Interaction of forskolin with voltage-gated K+ channels in PC12 cells.
Forskolin (FSK) directly blocks a distinct class of voltage-dependent K+ channels in pheochromocytoma cells. We have studied the biophysical mechanism of FSK action on these channels. The mean open duration decreased linearly with [FSK], indicating that a single molecule of FSK interacts with a single open K+ channel. FSK did not alter the voltage dependence of activation or the latency to first opening. Whole-cell currents in the presence of FSK did not show a rising phase in tail currents, suggesting that FSK-bound channels can close. We used a kinetic scheme in which FSK binds preferentially to the open state of the channel to describe its interaction with the K+ channel. This scheme is analogous to the modulated receptor hypothesis used to describe the interaction of local anesthetics with voltage-dependent Na+ channels.
Garber
S S
SS
Department of Neurobiology, Stanford University School of Medicine, California 94305.
Hoshi
T
T
Aldrich
R W
RW
D000310:Adrenal Gland Neoplasms; D000818:Animals; D005576:Colforsin / Q000378:metabolism / Q000494:pharmacology*; D004553:Electric Conductivity; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology*; D007700:Kinetics; D008012:Lidocaine / Q000494:pharmacology; D010673:Pheochromocytoma; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D011487:Protein Conformation; D051381:Rats; D014407:Tumor Cells, Cultured
D015221:Potassium Channels; D005576:Colforsin; D008012:Lidocaine