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A quantitative analysis of the activation and inactivation kinetics of HERG expressed in Xenopus oocytes.
J Physiol. 1997 Jul 01; 502 (Pt 1):45-60.JP

Abstract

1. The human ether à-go-go-related gene (HERG) encodes a K+ channel that is believed to be the basis of the delayed rectified current, IKr, in cardiac muscle. We studied HERG expressed in Xenopus oocytes using a two-electrode and cut-open oocyte clamp technique with [K+]0 of 2 and 98 mM. 2. The time course of activation of the channel was measured using an envelope of tails protocol and demonstrated that activation of the heterologously expressed HERG current (IHERG) was sigmoidal in onset. At least three closed states were required to reproduce the sigmoid time course. 3. The voltage dependence of the activation process and its saturation at positive voltages suggested the existence of at least one relatively voltage-insensitive step. A three closed state activation model with a single voltage-insensitive intermediate closed state was able to reproduce the time and voltage dependence of activation, deactivation and steady-state activation. Activation was insensitive to changes in [K+]0. 4. Both inactivation and recovery time constants increased with a change of [K+]0 from 2 to 98 mM. Steady-state inactivation shifted by approximately 30 mV in the depolarized direction with a change from 2 to 98 mM K+0. 5. Simulations showed that modulation of inactivation is a minimal component of the increase of this current by [K+]0, and that a large increase in total conductance must also occur.

Authors+Show Affiliations

Department of Medicine, Duke University Medical Center, Durham, NC, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo 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

9234196

Citation

Wang, S, et al. "A Quantitative Analysis of the Activation and Inactivation Kinetics of HERG Expressed in Xenopus Oocytes." The Journal of Physiology, vol. 502 (Pt 1), 1997, pp. 45-60.
Wang S, Liu S, Morales MJ, et al. A quantitative analysis of the activation and inactivation kinetics of HERG expressed in Xenopus oocytes. J Physiol. 1997;502 (Pt 1):45-60.
Wang, S., Liu, S., Morales, M. J., Strauss, H. C., & Rasmusson, R. L. (1997). A quantitative analysis of the activation and inactivation kinetics of HERG expressed in Xenopus oocytes. The Journal of Physiology, 502 (Pt 1), 45-60.
Wang S, et al. A Quantitative Analysis of the Activation and Inactivation Kinetics of HERG Expressed in Xenopus Oocytes. J Physiol. 1997 Jul 1;502 (Pt 1):45-60. PubMed PMID: 9234196.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A quantitative analysis of the activation and inactivation kinetics of HERG expressed in Xenopus oocytes. AU - Wang,S, AU - Liu,S, AU - Morales,M J, AU - Strauss,H C, AU - Rasmusson,R L, PY - 1997/7/1/pubmed PY - 1997/7/1/medline PY - 1997/7/1/entrez SP - 45 EP - 60 JF - The Journal of physiology JO - J Physiol VL - 502 (Pt 1) N2 - 1. The human ether à-go-go-related gene (HERG) encodes a K+ channel that is believed to be the basis of the delayed rectified current, IKr, in cardiac muscle. We studied HERG expressed in Xenopus oocytes using a two-electrode and cut-open oocyte clamp technique with [K+]0 of 2 and 98 mM. 2. The time course of activation of the channel was measured using an envelope of tails protocol and demonstrated that activation of the heterologously expressed HERG current (IHERG) was sigmoidal in onset. At least three closed states were required to reproduce the sigmoid time course. 3. The voltage dependence of the activation process and its saturation at positive voltages suggested the existence of at least one relatively voltage-insensitive step. A three closed state activation model with a single voltage-insensitive intermediate closed state was able to reproduce the time and voltage dependence of activation, deactivation and steady-state activation. Activation was insensitive to changes in [K+]0. 4. Both inactivation and recovery time constants increased with a change of [K+]0 from 2 to 98 mM. Steady-state inactivation shifted by approximately 30 mV in the depolarized direction with a change from 2 to 98 mM K+0. 5. Simulations showed that modulation of inactivation is a minimal component of the increase of this current by [K+]0, and that a large increase in total conductance must also occur. SN - 0022-3751 UR - https://www.unboundmedicine.com/medline/citation/9234196/A_quantitative_analysis_of_the_activation_and_inactivation_kinetics_of_HERG_expressed_in_Xenopus_oocytes_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0022-3751&date=1997&volume=502&spage=45 DB - PRIME DP - Unbound Medicine ER -