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Kinetic modulation of HERG potassium channels by the volatile anesthetic halothane.
Anesthesiology. 2002 Oct; 97(4):921-30.A

Abstract

BACKGROUND

(human ether-a-gogo related gene) encodes the cardiac rapidly activating delayed rectifier potassium currents (I(kr)), which play an important role in cardiac action potential repolarization. General anesthetics, like halothane, can prolong Q-T interval, suggesting that they act on myocellular repolarization, possibly involving HERG channels. Evidence for direct modulation of HERG channels by halothane is still lacking. To gain insight on HERG channel modulation by halothane the authors recorded macroscopic currents expressed in Xenopus oocytes and conducted non-stationary noise analysis to evaluate single channel parameters modified by the anesthetic.

METHODS

Macroscopic currents were recorded in 120 mM K(+) internal-5 mM K(+) external solutions with the cut open oocyte technique. Macropatch recordings for non-stationary noise analysis of HERG tail currents were made in symmetrical 120 mM K(+) solutions. Pulse protocols designed for HERG current recording were elicited from a holding potential of -80 mV. Halothane was delivered via gravity-fed perfusion.

RESULTS

Halothane (0.7%, 1.5%, and 3%) decreased macroscopic currents in a concentration-dependent manner (average reduction by 14%, 22%, and 35% in the range of -40 mV to 40 mV) irrespective of potential. HERG currents had slower activation and accelerated deactivation and inactivation. Non-stationary noise analysis revealed that halothane, 1.5%, decreased channel P(o) by 27%, whereas single-channel current amplitudes and number of channels in the patch remained unchanged.

CONCLUSIONS

Halothane inhibits HERG currents expressed in oocytes in a concentration-dependent manner. It slowed down activation and accelerated deactivation and inactivation of HERG channels. The authors' results demonstrate that halothane decreased HERG currents by modulating kinetic properties of HERG channels, decreasing their open probability. Partial block of I(kr) currents could contribute to delayed myocellular repolarization and altered cardiac electrophysiology.

Authors+Show Affiliations

Department of Anesthesiology, University of California, Los Angeles, The David Gefeen School of Medicine, 90095, USA.No affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

12357160

Citation

Li, Jichang, and Ana M. Correa. "Kinetic Modulation of HERG Potassium Channels By the Volatile Anesthetic Halothane." Anesthesiology, vol. 97, no. 4, 2002, pp. 921-30.
Li J, Correa AM. Kinetic modulation of HERG potassium channels by the volatile anesthetic halothane. Anesthesiology. 2002;97(4):921-30.
Li, J., & Correa, A. M. (2002). Kinetic modulation of HERG potassium channels by the volatile anesthetic halothane. Anesthesiology, 97(4), 921-30.
Li J, Correa AM. Kinetic Modulation of HERG Potassium Channels By the Volatile Anesthetic Halothane. Anesthesiology. 2002;97(4):921-30. PubMed PMID: 12357160.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Kinetic modulation of HERG potassium channels by the volatile anesthetic halothane. AU - Li,Jichang, AU - Correa,Ana M, PY - 2002/10/3/pubmed PY - 2002/10/31/medline PY - 2002/10/3/entrez SP - 921 EP - 30 JF - Anesthesiology JO - Anesthesiology VL - 97 IS - 4 N2 - BACKGROUND: (human ether-a-gogo related gene) encodes the cardiac rapidly activating delayed rectifier potassium currents (I(kr)), which play an important role in cardiac action potential repolarization. General anesthetics, like halothane, can prolong Q-T interval, suggesting that they act on myocellular repolarization, possibly involving HERG channels. Evidence for direct modulation of HERG channels by halothane is still lacking. To gain insight on HERG channel modulation by halothane the authors recorded macroscopic currents expressed in Xenopus oocytes and conducted non-stationary noise analysis to evaluate single channel parameters modified by the anesthetic. METHODS: Macroscopic currents were recorded in 120 mM K(+) internal-5 mM K(+) external solutions with the cut open oocyte technique. Macropatch recordings for non-stationary noise analysis of HERG tail currents were made in symmetrical 120 mM K(+) solutions. Pulse protocols designed for HERG current recording were elicited from a holding potential of -80 mV. Halothane was delivered via gravity-fed perfusion. RESULTS: Halothane (0.7%, 1.5%, and 3%) decreased macroscopic currents in a concentration-dependent manner (average reduction by 14%, 22%, and 35% in the range of -40 mV to 40 mV) irrespective of potential. HERG currents had slower activation and accelerated deactivation and inactivation. Non-stationary noise analysis revealed that halothane, 1.5%, decreased channel P(o) by 27%, whereas single-channel current amplitudes and number of channels in the patch remained unchanged. CONCLUSIONS: Halothane inhibits HERG currents expressed in oocytes in a concentration-dependent manner. It slowed down activation and accelerated deactivation and inactivation of HERG channels. The authors' results demonstrate that halothane decreased HERG currents by modulating kinetic properties of HERG channels, decreasing their open probability. Partial block of I(kr) currents could contribute to delayed myocellular repolarization and altered cardiac electrophysiology. SN - 0003-3022 UR - https://www.unboundmedicine.com/medline/citation/12357160/Kinetic_modulation_of_HERG_potassium_channels_by_the_volatile_anesthetic_halothane_ L2 - https://pubs.asahq.org/anesthesiology/article-lookup/doi/10.1097/00000542-200210000-00026 DB - PRIME DP - Unbound Medicine ER -