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Altered gating of HERG potassium channels by cobalt and lanthanum.
Pflugers Arch. 2000 Jun; 440(2):264-74.PA

Abstract

Activation of the rapid, delayed rectifier K current (IKr) is important for normal repolarization of cardiac action potentials, especially in mammalian ventricular muscle. The study of this current has been greatly aided by the discovery that the human ether-a-go-go-related gene (HERG) encodes the pore-forming alpha subunits of these channels. As for other voltage-activated K+ channels, divalent and trivalent cations affect the gating of HERG channels by screening negative membrane surface charges or by direct interaction with the channel gating mechanism. Previous studies have reported that IKr of myocytes, and HERG channels heterologously expressed in Xenopus oocytes, are reduced by external Co2+ and La3+. We have reinvestigated the "blocking" effect of Co2+ and La3+ on HERG channels expressed in Xenopus oocytes. At concentrations previously reported to block IKr or HERG current (IHERG), Co2+ (10 mM) and La3+ (10 microM) had only small effects on the magnitude of fully activated IHERG. The apparent block results from altered kinetics and voltage dependence of gating, similar to the effects of Ca2+ on HERG channels. Under control conditions, the half-points for voltage-dependent activation and inactivation of HERG were -35+/-2.1 and -76.3+/-1.7 mV, respectively. Co2+ and La3+ accelerated the rate of deactivation, decreased the rate of current activation, and shifted the half-point of the HERG channel activation curve by +53 and +65 mV, respectively. Co2+ shifted the voltage dependence of inactivation by + 14 mV, whereas La3+ had no effect. Co2+ also slowed the onset of IHERG inactivation and accelerated the rate of recovery from inactivation. These results indicate that reduction of IHERG by Co2+ (10 mM) and La3+ (10 microM) during depolarizing pulses is caused by a positive shift in the voltage dependence of activation, and does not result from pore block.

Authors+Show Affiliations

Unidad de Investigacion Carlos Méndez, CUIB, Universidad de Colima, Mexico. sancheza@cgic.ucol.mxNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

10898527

Citation

Sanchez-Chapula, J A., and M C. Sanguinetti. "Altered Gating of HERG Potassium Channels By Cobalt and Lanthanum." Pflugers Archiv : European Journal of Physiology, vol. 440, no. 2, 2000, pp. 264-74.
Sanchez-Chapula JA, Sanguinetti MC. Altered gating of HERG potassium channels by cobalt and lanthanum. Pflugers Arch. 2000;440(2):264-74.
Sanchez-Chapula, J. A., & Sanguinetti, M. C. (2000). Altered gating of HERG potassium channels by cobalt and lanthanum. Pflugers Archiv : European Journal of Physiology, 440(2), 264-74.
Sanchez-Chapula JA, Sanguinetti MC. Altered Gating of HERG Potassium Channels By Cobalt and Lanthanum. Pflugers Arch. 2000;440(2):264-74. PubMed PMID: 10898527.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Altered gating of HERG potassium channels by cobalt and lanthanum. AU - Sanchez-Chapula,J A, AU - Sanguinetti,M C, PY - 2000/7/18/pubmed PY - 2001/2/28/medline PY - 2000/7/18/entrez SP - 264 EP - 74 JF - Pflugers Archiv : European journal of physiology JO - Pflugers Arch VL - 440 IS - 2 N2 - Activation of the rapid, delayed rectifier K current (IKr) is important for normal repolarization of cardiac action potentials, especially in mammalian ventricular muscle. The study of this current has been greatly aided by the discovery that the human ether-a-go-go-related gene (HERG) encodes the pore-forming alpha subunits of these channels. As for other voltage-activated K+ channels, divalent and trivalent cations affect the gating of HERG channels by screening negative membrane surface charges or by direct interaction with the channel gating mechanism. Previous studies have reported that IKr of myocytes, and HERG channels heterologously expressed in Xenopus oocytes, are reduced by external Co2+ and La3+. We have reinvestigated the "blocking" effect of Co2+ and La3+ on HERG channels expressed in Xenopus oocytes. At concentrations previously reported to block IKr or HERG current (IHERG), Co2+ (10 mM) and La3+ (10 microM) had only small effects on the magnitude of fully activated IHERG. The apparent block results from altered kinetics and voltage dependence of gating, similar to the effects of Ca2+ on HERG channels. Under control conditions, the half-points for voltage-dependent activation and inactivation of HERG were -35+/-2.1 and -76.3+/-1.7 mV, respectively. Co2+ and La3+ accelerated the rate of deactivation, decreased the rate of current activation, and shifted the half-point of the HERG channel activation curve by +53 and +65 mV, respectively. Co2+ shifted the voltage dependence of inactivation by + 14 mV, whereas La3+ had no effect. Co2+ also slowed the onset of IHERG inactivation and accelerated the rate of recovery from inactivation. These results indicate that reduction of IHERG by Co2+ (10 mM) and La3+ (10 microM) during depolarizing pulses is caused by a positive shift in the voltage dependence of activation, and does not result from pore block. SN - 0031-6768 UR - https://www.unboundmedicine.com/medline/citation/10898527/Altered_gating_of_HERG_potassium_channels_by_cobalt_and_lanthanum_ L2 - https://dx.doi.org/10.1007/s004240000263 DB - PRIME DP - Unbound Medicine ER -