Rapid electrical stimulation of contraction modulates gap junction protein in neonatal rat cultured cardiomyocytes: Involvement of mitogen-activated protein kinases and effects of angiotensin ii-receptor antagonist Original Research Article

Objectives The aim of this study was to investigate the effects of rapid electrical stimulation (RES) of contraction on the expression of connexin (Cx)43 gap junction in neonatal rat cultured ventricular myocytes and the consequent changes of conduction properties. Background The expression and distribution of gap junctions in cardiac muscle can be changed readily under a variety of pathological conditions because of dynamic turnover of Cxs. The effects of RES of contraction on gap junction remodeling are not well understood. Methods Neonatal rat ventricular myocytes cultured for five days were subjected to RES (field stimulation) at 3.0 Hz for up to 120 min. Results Rapid electrical stimulation resulted in a significant upregulation of Cx43 (by not, vert, similar1.5-fold in protein and by not, vert, similar1.9-fold in messenger ribonucleic acid at 60 min). Immunoreactive signal of Cx43 was also increased. Angiotensin II (AngII) content was increased significantly by RES >15 min. Phosphorylated forms of extracellular signal-regulated protein kinase (ERK), c-Jun NH2-terminal kinases, and p38 mitogen-activated protein kinases (MAPKs) were all increased dramatically by RES with peaks at 5 not, vert, similar 60 min. Propagation of excitation was visualized by extracellular potential mapping by using a multiple electrode array system. Conduction velocity was increased significantly by RES for 60 to 90 min (25% not, vert, similar 27% increase). Treatment of myocytes with losartan (100 nmol/l) prevented most of these effects of RES; RES-induced upregulation of Cx43 was also prevented by specific inhibitors for ERK and p38 MAPKs. Conclusions A short-term RES causes upregulation of Cx43 in cardiomyocytes and a concomitant increase of conduction velocity, mainly through an autocrine action of AngII to activate ERK and p38 MAPKs.