Journal of Neuroscience, Vol 10, 3361-3368, Copyright © 1990 by Society for Neuroscience
Interaction of forskolin with voltage-gated K+ channels in PC12 cells
SS Garber, T Hoshi and RW Aldrich
Department of Neurobiology, Stanford University School of Medicine, California 94305.
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.