Cyclic GMP inhibits and shifts the activation curve of the delayed-rectifier (I[K1]) of type I mammalian vestibular hair cells

Abstract

NITRIC oxide (NO) plays a role in the modulation of the predominant potassium current of type I vestibular hair cells, a low-voltage activated current called I(K1). Since many effects of NO are mediated via cGMP, patch-clamp recordings were made to evaluate the effects of cGMP on I(K1). In whole-cell recordings 1 mM cGMP shifted Vhalf of I(K1) by 15.0 +/- 2.4 mV (n = 6) to more positive. In cell-attached 'multichannel' recordings 1 mM 8-bromo-cGMP caused a reversible shift of Vhalf by 13.8 +/- 2.6 mV (n = 12) and in single channel recordings in the cell-attached configuration the open probability was reduced at -60 mV from 0.39 +/- 0.14 to 0.08 +/- 0.01. cGMP had no effect on excised inside-out patches, indicating that an intact cytosolic milieu with functioning phosphorylation cascades is necessary. cGMP seems to be an important second messenger which reduces the potassium conductance of vestibular hair cells.