Title: A repolarization-induced transient increase in the outward current of the inward rectifier K^+ channel in guinea-pig cardiac myocytes
Abstract: The inwardly rectifying K+ current (IKir), historically termed IK1 in the heart, maintains the resting membrane potentials of ventricular myocytes and Purkinje fibres near the equilibrium potential for K+ (EK). During the action potentials, IKir in these cells flows outwardly only in the voltage range near EK due to its strong inward rectification. This flow of outward IKir, however, is important for the final repolarization of the action potentials (Noble, 1975; Giles & Imaizumi, 1988; Carmeliet, 1993). The reduction of outward IKir caused by low external [K+] or external Cs+ block has been shown to result in a retardation of normal repolarization (early after-depolarization), which in turn induces ventricular tachiarrythmias (Cranefield & Aronson, 1988).
The channel gating causing the strong rectification of IKir (Carmeliet, 1982; Kurachi, 1985; Tourneur, Mitra, Morad & Rougier, 1987; Ishihara, Mitsuiye, Noma & Takano, 1989; Silver & DeCoursey, 1990; Stanfield et al. 1994) is now accounted for by the voltage-dependent blockage of the channel by intracellular polyamines (spermine/spermidine) (Lopatin, Makhina & Nichols, 1994; Ficker, Taglialatela, Wible, Henley & Brown, 1994; Lopatin, Makhina & Nichols, 1995; Ishihara, Hiraoka & Ochi, 1996; Lopatin & Nichols, 1996). Cytoplasmic Mg2+ has also been shown to block the outward current of the inwardly rectifying K+ (KIR) channels (Matsuda, Saigusa & Irisawa, 1987; Vandenberg, 1987). Under physiological conditions, it has been suggested that blockage of the channel by Mg2+ occurs at depolarized voltage levels, while spermine block takes place in the voltage range near EK (Ishihara et al. 1989, 1996). The role of the Mg2+ block, however, is unclear since the channel can exhibit a strong inward rectification in the absence of Mg2+ (Ishihara et al. 1989; Silver & DeCoursey, 1990; Stanfield et al. 1994).
By studying the cloned KIR channel IRK1 (Kir2.1), we recently found that the fast relief of Mg2+ block increases the outward current of IKir flowing during membrane repolarization (Ishihara, 1997). Since repolarization of cardiac action potentials is caused by a small net outward current (Cranefield & Aronson, 1988), we studied whether or not the same current component flows in cardiac myocytes. We show here that the outward current of native cardiac IKir transiently increases upon repolarization due to the relief of Mg2+ block and the subsequent gating process presumably caused by the polyamine block. Observations on this current component suggest that alterations of outward IKir amplitude modulate the repolarization phase of the cardiac action potentials under physiological and pathological conditions.
Publication Year: 1999
Publication Date: 1999-08-31
Language: en
Type: article
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Cited By Count: 13
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