Electrophysiological Analysis of Voltage-Gated Ion Channel Modulation by General Anesthetics

Methods Enzymol. 2018:602:339-368. doi: 10.1016/bs.mie.2018.01.013. Epub 2018 Mar 15.

Abstract

Voltage-gated ion channels (VGICs) of excitable tissues are emerging as targets likely involved in both the therapeutic and toxic effects of inhaled and intravenous general anesthetics. Whereas sevoflurane and propofol inhibit voltage-gated Na+ channels (Navs), sevoflurane potentiates certain voltage-gated K+ channels (Kvs). The combination of these effects would dampen neural excitability and, therefore, might contribute to the clinical endpoints of general anesthesia. As the body of work regarding the interaction of general anesthetics with VGICs continues to grow, a multidisciplinary approach involving functional, biochemical, structural, and computational techniques, many of which are detailed in other chapters, has increasingly become necessary to solve the molecular mechanism of general anesthetic action on VGICs. Here, we focus on electrophysiological and modeling approaches and methodologies to describe how our work has elucidated the biophysical basis of the inhibition Navs by propofol and the potentiation of Kvs by sevoflurane.

Keywords: Gating modulation; Kv channel; Nav channel; Patch clamping; Propofol; Sevoflurane; Voltage clamping.

MeSH terms

  • Anesthetics, General / pharmacology*
  • Animals
  • Cell Culture Techniques / instrumentation
  • Cell Culture Techniques / methods
  • Computer Simulation
  • Electrodes
  • Electrophysiology / instrumentation
  • Electrophysiology / methods*
  • HEK293 Cells
  • Humans
  • Ion Channel Gating / drug effects*
  • Ion Channel Gating / physiology
  • Models, Biological
  • Oocytes
  • Patch-Clamp Techniques / instrumentation
  • Patch-Clamp Techniques / methods
  • Potassium Channels, Voltage-Gated / agonists
  • Potassium Channels, Voltage-Gated / metabolism*
  • Propofol / pharmacology
  • Recombinant Proteins / metabolism
  • Sevoflurane / pharmacology
  • Transfection / instrumentation
  • Transfection / methods
  • Voltage-Gated Sodium Channel Blockers / pharmacology
  • Voltage-Gated Sodium Channels / metabolism*
  • Xenopus laevis

Substances

  • Anesthetics, General
  • Potassium Channels, Voltage-Gated
  • Recombinant Proteins
  • Voltage-Gated Sodium Channel Blockers
  • Voltage-Gated Sodium Channels
  • Sevoflurane
  • Propofol