NFATc3-dependent loss of I(to) gradient across the left ventricular wall during chronic beta adrenergic stimulation.

ABSTRACT: In heart, pore-forming Kv4 alpha channel subunits underlie the K(+) transient outward current (I(to)). Expression of Kv4 is greater in left ventricular epicardial (EPI) than in endocardial (ENDO) cells, resulting in larger I(to) in EPI than in ENDO cells. In adult ventricular myocytes, the transcription factor NFATc3 suppresses Kv4 expression. NFATc3 activity is higher in ENDO than in EPI cells and this has been proposed to contribute to heterogeneous Kv4 expression across the left ventricular free wall. Here, we tested the hypothesis that regional activation of NFATc3 signaling dissipates the gradient of I(to) density across the mouse left ventricle during chronic activation of beta adrenergic signaling. [Ca(2+)](i), calcineurin, and NFAT activity were larger in ENDO than in EPI myocytes.

SUBMITTER: Rossow CF 

PROVIDER: S-EPMC2664558 | biostudies-literature | 2009 Feb

REPOSITORIES: biostudies-literature