Compensatory role of CaMKII on I-Ca and SR function during acidosis in ratventricular myocytes

It has been suggested that the activity of Ca2+/calmodulin-dependent protei n kinase II (CaMKII) increases during acidosis in cardiac muscle. Thus we h ave investigated the role of CaMKII during acidosis by monitoring intracell ular Ca2+ (using fura-2) and I-Ca (Using the perforated patch clamp techniq ue) during acidosis, in the absence and presence of the CaMKII inhibitor KN -93, in rat isolated ventricular myocytes. In the absence of KN-93, acidosi s (pH 6.5) increased the amplitude of the fura-2 transient and prolonged it s decay, but in the presence of KN-93 acidosis did not alter the amplitude and prolonged the decay more. In the absence of KN-93, acidosis increased t he amplitude of the caffeine-induced fura-2 transient but did not alter its amplitude in the presence of KN-93. I-Ca did not change significantly duri ng acidosis in the absence of KN-93 but decreased during acidosis in the pr esence of KN-93. These results suggest that activation of CaMKII during aci dosis helps to compensate for the direct inhibitory effects of acidosis on sarcoplasmic reticular Ca2+ uptake and I-Ca.