Tags

Type your tag names separated by a space and hit enter

Blockade of HERG channels expressed in Xenopus laevis oocytes by external divalent cations.
Biophys J. 1999 Apr; 76(4):1959-71.BJ

Abstract

We have investigated actions of various divalent cations (Ba2+, Sr2+, Mn2+, Co2+, Ni2+, Zn2+) on human ether-a-go-go related gene (HERG) channels expressed in Xenopus laevis oocytes using the voltage clamp technique. All divalent cations inhibited HERG current dose-dependently in a voltage-dependent manner. The concentration for half-maximum inhibition (Ki) decreased at more negative potentials, indicating block is facilitated by hyperpolarization. Ki at 0 mV for Zn2+, Ni2+, Co2+, Ba2+, Mn2+, and Sr2+ was 0.19, 0.36, 0. 50, 0.58, 2.36, and 6.47 mM, respectively. The effects were manifested in four ways: 1) right shift of voltage dependence of activation, 2) decrease of maximum conductance, 3) acceleration of current decay, and 4) slowing of activation. However, each parameter was not affected by each cation to the same extent. The potency for the shift of voltage dependence of activation was in the order Zn2+ > Ni2+ >/= Co2+ > Ba2+ > Mn2+ > Sr2+, whereas the potency for the decrease of maximum conductance was Zn2+ > Ba2+ > Sr2+ > Co2+ > Mn2+. The kinetics of activation and deactivation were also affected, but the two parameters are not affected to the same extent. Slowing of activation by Ba2+ was most distinct, causing a marked initial delay of current onset. From these results we concluded that HERG channels are nonselectively blocked by most divalent cations from the external side, and several different mechanism are involved in their actions. There exist at least two distinct binding sites for their action: one for the voltage-dependent effect and the other for reducing maximum conductance.

Authors+Show Affiliations

Department of Physiology, Seoul National University College of Medicine, Seoul 110-799, Republic of Korea. wonkyung@plaza.snu.ac.krNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

10096894

Citation

Ho, W K., et al. "Blockade of HERG Channels Expressed in Xenopus Laevis Oocytes By External Divalent Cations." Biophysical Journal, vol. 76, no. 4, 1999, pp. 1959-71.
Ho WK, Kim I, Lee CO, et al. Blockade of HERG channels expressed in Xenopus laevis oocytes by external divalent cations. Biophys J. 1999;76(4):1959-71.
Ho, W. K., Kim, I., Lee, C. O., Youm, J. B., Lee, S. H., & Earm, Y. E. (1999). Blockade of HERG channels expressed in Xenopus laevis oocytes by external divalent cations. Biophysical Journal, 76(4), 1959-71.
Ho WK, et al. Blockade of HERG Channels Expressed in Xenopus Laevis Oocytes By External Divalent Cations. Biophys J. 1999;76(4):1959-71. PubMed PMID: 10096894.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Blockade of HERG channels expressed in Xenopus laevis oocytes by external divalent cations. AU - Ho,W K, AU - Kim,I, AU - Lee,C O, AU - Youm,J B, AU - Lee,S H, AU - Earm,Y E, PY - 1999/3/30/pubmed PY - 1999/3/30/medline PY - 1999/3/30/entrez SP - 1959 EP - 71 JF - Biophysical journal JO - Biophys J VL - 76 IS - 4 N2 - We have investigated actions of various divalent cations (Ba2+, Sr2+, Mn2+, Co2+, Ni2+, Zn2+) on human ether-a-go-go related gene (HERG) channels expressed in Xenopus laevis oocytes using the voltage clamp technique. All divalent cations inhibited HERG current dose-dependently in a voltage-dependent manner. The concentration for half-maximum inhibition (Ki) decreased at more negative potentials, indicating block is facilitated by hyperpolarization. Ki at 0 mV for Zn2+, Ni2+, Co2+, Ba2+, Mn2+, and Sr2+ was 0.19, 0.36, 0. 50, 0.58, 2.36, and 6.47 mM, respectively. The effects were manifested in four ways: 1) right shift of voltage dependence of activation, 2) decrease of maximum conductance, 3) acceleration of current decay, and 4) slowing of activation. However, each parameter was not affected by each cation to the same extent. The potency for the shift of voltage dependence of activation was in the order Zn2+ > Ni2+ >/= Co2+ > Ba2+ > Mn2+ > Sr2+, whereas the potency for the decrease of maximum conductance was Zn2+ > Ba2+ > Sr2+ > Co2+ > Mn2+. The kinetics of activation and deactivation were also affected, but the two parameters are not affected to the same extent. Slowing of activation by Ba2+ was most distinct, causing a marked initial delay of current onset. From these results we concluded that HERG channels are nonselectively blocked by most divalent cations from the external side, and several different mechanism are involved in their actions. There exist at least two distinct binding sites for their action: one for the voltage-dependent effect and the other for reducing maximum conductance. SN - 0006-3495 UR - https://www.unboundmedicine.com/medline/citation/10096894/Blockade_of_HERG_channels_expressed_in_Xenopus_laevis_oocytes_by_external_divalent_cations_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-3495(99)77355-8 DB - PRIME DP - Unbound Medicine ER -