Acidosis-induced p38 MAPK activation and its implication in regulation of cardiac contractility.
AIM
To determine the possible role of pH in mediating activation of p38 mitogen-activated protein kinase (MAPK) and the consequent function of activated p38 MAPK in regulating cardiac contractility.


METHODS
Adult rat cardiomyocytes were isolated and cultured. Low pH media was used to induce intracellular acidosis and contraction of single cardiomyocyte was measured.


RESULTS
Phosphorylation of p38 MAPK was increased during ischemia, and pHi was decreased. Intracellular acidosis activated p38 MAPK to a similar level as ischemia. Inhibition of p38 MAPK activation by SB203580, a specific inhibitor of p38 MAPK, reversed acidosis-mediated reduction of myocyte contractility.


CONCLUSION
In adult rat cardiomyocytes, intracellular acidification activated p38 MAPK and decreased cardiac contractility. Pretreatment of cardiomyocytes with SB203580 completely blocked p38 MAPK activation and partially reversed acidosis-mediated decline of cardiac contractility.