Depression by isoflurane of the action potential and underlying voltage-gated ion currents in isolated rat neurohypophysial nerve terminals

The Journal of Pharmacology and Experimental Therapeutics
Wei Ouyang, H C Hemmings

Abstract

We characterized the effects of the volatile anesthetic isoflurane on the ion currents that contribute to the action potential (AP) in isolated rat neurohypophysial (NHP) nerve terminals using patch-clamp electrophysiology. Mean resting membrane potential and AP amplitude were -62.3 +/- 4.1 and 69.2 +/- 2.9 mV, respectively, in NHP terminals. Two components of outward K(+) current (I(K)) were identified in voltage-clamp recordings: a transient I(K) and a sustained I(K) with minimal inactivation. Some terminals displayed a slowly activating I(K), probably the big Ca(2+)-activated K(+) current (BK). Isoflurane reversibly inhibited AP amplitude and increased AP half-width in normal extracellular Ca(2+) (2.2 mM). In high extracellular Ca(2+) (10 mM), isoflurane also reduced the afterhypolarization peak amplitude. A transient tetrodotoxin-sensitive Na(+) current (I(Na)) was the principal current mediating the depolarizing phase of the AP. A slowly inactivating Cd(2+)-sensitive current (probably a voltagegated Ca(2+) current; I(Ca)) followed the initial I(Na). Isoflurane reversibly inhibited both I(Na) and I(Ca) elicited by a voltage-stimulus based on an averaged AP waveform. The isoflurane IC(50) for AP waveform-evoked I(Na) was 0.3...Continue Reading

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Citations

Jun 11, 2009·British Journal of Anaesthesia·H C Hemmings
Apr 23, 2014·Proceedings of the National Academy of Sciences of the United States of America·Annika F BarberManuel Covarrubias
Sep 10, 2015·Proceedings of the National Academy of Sciences of the United States of America·Joel P BaumgartHugh C Hemmings
Jun 20, 2015·British Journal of Anaesthesia·K PurtellH C Hemmings
Nov 3, 2012·Environmental Toxicology and Pharmacology·Xiao-lin XuLi-chun Xu
Jul 28, 2015·Autonomic Neuroscience : Basic & Clinical·S L JohansenM B Harris
Jul 24, 2010·Korean journal of anesthesiology·Yong Son
Jun 23, 2007·Anesthesiology·Wei OuYang, Hugh C Hemmings
May 3, 2008·Canadian Journal of Anaesthesia = Journal Canadien D'anesthésie·Chin C ChuJhi J Wang
Feb 25, 2005·Molecular Pharmacology·Hugh C HemmingsTimothy A Ryan
Sep 22, 2005·The Journal of Pharmacology and Experimental Therapeutics·Robert I Westphalen, Hugh C Hemmings
Jun 16, 2007·The Journal of Pharmacology and Experimental Therapeutics·Wei OuyangHugh C Hemmings
Apr 10, 2018·Frontiers in Neuroscience·Bhedita J SeewooJennifer Rodger
Feb 9, 2011·Radiation Research·J KnudsenO Hyldegaard
Sep 1, 2019·Pharmacological Reviews·Nicholas DenommeGeorge A Mashour
Feb 29, 2020·Current Neuropharmacology·Xuechao HaoCheng Zhou

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