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Isolation of Human Atrial Myocytes for Simultaneous Measurements of Ca2+ Transients and Membrane Currents
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Halothane inhibition of recombinant cardiac L-type Ca2+ channels expressed in HEK-293 cells

Kevin J Gingrich1, Son Tran, Igor M Nikonorov

  • 1Department of Anesthesiology, New York University School of Medicine, 550 First Avenue, New York, NY 10016, USA. kevin.gingrich@med.nyu.edu

Anesthesiology
|November 25, 2005
PubMed

Insights

Volatile anesthetics like halothane inhibit cardiac L-type calcium channels. The alpha2/delta1 subunit significantly enhances this effect by altering channel states at resting membrane potential.

Area of Science:

  • Cardiology
  • Pharmacology
  • Molecular Biology

Background:

  • Volatile anesthetics depress cardiac contractility by inhibiting cardiac L-type calcium channels.
  • Understanding the role of voltage-dependent inactivation is crucial for anesthetic drug development.

Purpose of the Study:

  • To investigate the impact of the alpha2/delta1 subunit on halothane's inhibition of cardiac L-type calcium channels.
  • To elucidate the mechanisms underlying halothane's effects on channel function and transmembrane charge transfer.

Main Methods:

  • Recombinant cardiac L-type calcium channel subunits (alpha1Cbeta2a and alpha1Cbeta2aalpha2/delta1) were expressed in HEK-293 cells.
  • Patch clamp electrophysiology was used to record macroscopic barium currents and assess halothane's effects.
  • Cells were identified for patch-clamp recording via fluorescence microscopy.

Main Results:

  • Halothane inhibited peak current (I(peak)) and enhanced inactivation in a concentration-dependent manner for both channel types.
  • Coexpression of alpha2/delta1 significantly increased halothane's potency for inhibiting I(peak) and inactivation.
  • Halothane reduced transmembrane charge transfer primarily through I(peak) depression, not enhanced inactivation.

Conclusions:

  • Phenotypic features conferred by the alpha2/delta1 subunit are critical for halothane's inhibition of cardiac L-type calcium channels.
  • Halothane's primary mechanism involves depression of I(peak) due to transitions to nonactivatable states at resting potentials.
  • The study highlights the importance of resting membrane potential states in halothane's action, discounting the role of inactivation in charge transfer reduction.
Abstract

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