Effects of Mg2+ on basal and beta-adrenergic-stimulated delayed rectifier potassium current in frog atrial myocytes.

1. The effects of internal Mg2+ ions on the delayed rectifier potassium current (IK) of bull-frog atrial myocytes were studied using the whole-cell configuration of the patch-clamp technique with a perfusable patch electrode. 2. Initial variations in IK amplitude were dependent on [Mg2+]i. With [Mg2+] greater than 1 mM, the amplitude of IK usually decreased after initiating the whole-cell recording configuration (run-down); with [Mg2+]i less than 1 mM, IK usually increased (run-up). Mg2+ blocked IK with an apparent half-maximal effect of 0.6 mM [Mg2+]i. 3. The basal free [Mg2+]i, indicated by the amplitude of IK before run-up or run-down, was estimated from the relationship between [Mg2+]i and IK to be 0.8 mM. 4. The amplitude of both the activation curve and the instantaneous voltage-current relationship was decreased by increasing [Mg2+]i. Under these conditions, the voltage dependence of IK was not affected. 5. The rate of activation of the current at +40 mV was slowed by increasing [Mg2+]i with little effect on the rate of deactivation at -50 mV. This is in contrast to the effects of isoprenaline, which speeded activation and slowed deactivation. 6. Isoprenaline increased IK on average by about 2.5 pA/pF, whether IK had previously run down or not, and regardless of [Mg2+]i. The reversibility of isoprenaline was partially inhibited at [Mg2+]i less than 1 mM. 7. It is concluded that Mg2+ affects IK via several mechanisms that might include a Mg(2+)-dependent phosphatase.