Intracellular Ca modulates K-inward rectification in cardiac myocytes

In cardiac myocytes, instantaneous inward rectification of the K-rectifying channel is abolished by removal of divalent cations from the intracellular environment and can be restored by addition of Mg ions at submillimolar concentrations, which has led to the proposal that Mg ions regulate inward rectification in these cells (Matsuda et al., 1987; Vandenberg, 1987; Matsuda, 1988). Here we report that Ca, too, reduces outward current flow through single inward rectifier channels in cell-free inside-out patches at much lower (submicromolar) concentrations. Intracellular Ca induces rectification by decreasing the probability of the main open channel state and by favouring the opening of channel substrates. Ca concentrations generating rectification are in the range of the Ca transient during activity, suggesting that Ca ions can contribute to K-rectification during cardiac muscle contraction.