Abstract
We investigated the actions of various divalent cations on the delayed rectifier K+ currents (I Kr) in rabbit sinoatrial node cells using the whole-cell voltage-clamp technique in isotonic K+ solutions. External divalent cations decreased the amplitude of currents, accelerated the time course of deactivation and shifted the activation to positive potentials in a dose-dependent manner. The concentrations for half-maximum inhibition of the steady-state currents (K M) obtained at 0 mV were 0.63, 1.36, 1.65 and 2.16 mM for Ni2+, Co2+, Mn2+ and Ba2+, respectively. The effect was voltage dependent (K M decreased e-fold for 12.2–16.8 mV hyperpolarization), but the dependence did not vary significantly among different cations. Acceleration of the time course of current deactivation by the increase of divalent cation concentration was well fitted by the voltage-dependent block model, and the binding rate constant (k 1) was obtained. The binding rates for the ions took the following order: Ni2+ >Co2+ >Mn2+ >Ba2+. The degree of the shift of activation occurred in the same order: Ni2+ >Co2+ >Mn2+ >Ba2+. From these results, we conclude that I Kr channels are non-selectively blocked by most divalent cations from the external side and that the binding site is located deep inside the channel, resulting in a steep voltage dependence of the blockade.
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Received: 26 January 1999 / Received after revision: 16 March 1999 / Accepted: 18 March 1999
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Song, DK., Earm, Y. & Ho, WK. Blockade of the delayed rectifier K+ currents, I Kr, in rabbit sinoatrial node cells by external divalent cations. Pflügers Arch 438, 147–153 (1999). https://doi.org/10.1007/s004240050892
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DOI: https://doi.org/10.1007/s004240050892