Intracellular Mg2+ depletion depresses the delayed rectifier K+ current in guinea pig ventricular myocytes.

The effects of various [Mg2+]i, particularly low [Mg2+]i, on the delayed rectifier K+ current (IK) were studied in guinea pig ventricular myocytes with the patch clamp technique. The magnitude of IK was evaluated from the amplitude of its tail current elicited on repolarization following the depolarizing steps. The pipette-perfusion technique was also used. The initial variations of IK magnitude were dependent on [Mg2+]i in the internal solutions with which the whole-cell recording was begun. With 0.03 to 1 mM [Mg2+]i, IK was relatively stable after patch rupture, showing a minimal decay with time; with 3 mM [Mg2+]i, IK rapidly declined; with [Mg2+]i, less than 0.01 mM IK transiently increased after patch break, but declined progressively thereafter as the magnitude of IK decreased to about 30% of the initial magnitude in 10 min. The decline of IK at low [Mg2+]i showed the following features. The decline was accompanied little by changes in the voltage-activation relation or by changes in the kinetics of current deactivation. The decline was not related to changes in [Ca2+]i and was also observed in ATP gamma S-loaded, isoprenaline-stimulated cells, in which IK channels were presumed to be persistently phosphorylated. An application of okadaic acid did not prevent the decline of IK during Mg2+ depletion. It is suggested that a presence of [Mg2+]i higher than 0.01 mM is required to maintain IK in guinea pig ventricular cells. The depression of IK at low [Mg2+]i appears to involve a phosphorylation-dephosphorylation-independent mechanism.