The Inhibition of the Small-Conductance Ca(2+)-Activated Potassium Channels Decreases the Sinus Node Pacemaking during Beta-Adrenergic Activation

Sinus pacemaking is based on tight cooperation of intracellular Ca(2+) handling and surface membrane ion channels. An important player of this synergistic crosstalk could be the small-conductance Ca(2+)-activated K(+)-channel (I(SK)) that could contribute to the sinoatrial node (SAN) pacemaking driven by the intracellular Ca(2+) changes under normal conditions and beta-adrenergic activation, however, the exact role is not fully clarified. SK2 channel expression was verified by immunoblot technique in rabbit SAN cells. Ionic currents and action potentials were measured by patch-clamp technique. The ECG R-R intervals were obtained by Langendorff-perfusion method on a rabbit heart. Apamin, a selective inhibitor of SK channels, was used during the experiments. Patch-clamp experiments revealed an apamin-sensitive current. When 100 nM apamin was applied, we found no change in the action potential nor in the ECG R-R interval. In experiments where isoproterenol was employed, apamin increased the cycle length of the SAN action potentials and enhanced the ECG R-R interval. Apamin did not amplify the cycle length variability or ECG R-R interval variability. Our data indicate that I(SK) has no role under normal condition, however, it moderately contributes to the SAN automaticity under beta-adrenergic activation.