AKAP150‐dependent changes in K v channel expression in ventricular myocytes following myocardial infarction

AKAP150 is anchoring protein that plays important role in compartmentalizing protein kinase A and calcineurin signaling to specific sarcolemmal domains in cardiomyocyte. Increased β ‐ adrenergic signaling after myocardial infarction (MI) triggers activation of the Ca 2+ ‐dependent phosphatase calcineurin and the transcription factor NFATc3, resulting in down‐regulation of voltage‐gated K + (K V ) channel in ventricular myocytes. Here we tested the hypothesis that AKAP150 targeting of calcineurin to the sarcolemma is required for NFATc3 activation and the subsequent down‐regulation of K V currents observed after MI. We found that ablation of AKAP150 decreased NFATc3 nuclear translocation and was protective against down‐regulation of K V currents after MI. To investigate the role of AKAP150‐associated calcineurin in the regulation of K v channel expression; we investigated the effects of MI on ventricular myocytes of a mouse genetically engineered to express an AKAP150 that lacks its binding site for calcineurin (AKAP150 Δ CaN). The amplitude of K v currents was decreased in WT, but not in AKAP150 Δ CaN cardiomyocytes after MI. These data suggest that targeting of calcineurin to the sarcolemma of ventricular myocytes by AKAP150 is critical for the activation of calcineurin/NFATc3 signaling pathway and the down regulation of K V currents after MI.