Single-channel basis for conductance increase induced by isoflurane in Shaker H4 IR K(+) channels.
Volatile anesthetics modulate the function of various K(+) channels. We previously reported that isoflurane induces an increase in macroscopic currents and a slowing down of current deactivation of Shaker H4 IR K(+) channels. To understand the single-channel basis of these effects, we performed nonstationary noise analysis of macroscopic currents and analysis of single channels in patches from Xenopus oocytes expressing Shaker H4 IR. Isoflurane (1.2% and 2.5%) induced concentration-dependent, partially reversible increases in macroscopic currents and in the time course of tail currents. Noise analysis of currents (70 mV) revealed an increase in unitary current (approximately 17%) and maximum open probability (approximately 20%). Single-channel conductance was larger (approximately 20%), and opening events were more stable, in isoflurane. Tail-current slow time constants increased by 41% and 136% in 1.2% and 2.5% isoflurane, respectively. Our results show that, in a manner consistent with stabilization of the open state, isoflurane increased the macroscopic conductance of Shaker H4 IR K(+) channels by increasing the single-channel conductance and the open probability.
Li
J
J
Department of Anesthesiology, School of Medicine, University of California, Los Angeles, California 90095-7115, USA.
Correa
A M
AM
D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology; D005260:Female; D066298:In Vitro Techniques; D007530:Isoflurane / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009865:Oocytes / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D018075:RNA, Complementary; D011994:Recombinant Proteins / Q000187:drug effects / Q000378:metabolism; D051637:Shaker Superfamily of Potassium Channels; D014158:Transcription, Genetic; D014982:Xenopus laevis
D015221:Potassium Channels; D018075:RNA, Complementary; D011994:Recombinant Proteins; D051637:Shaker Superfamily of Potassium Channels; D007530:Isoflurane