Compensatory role of CaMKII on I _Ca and SR function during acidosis in rat ventricular myocytes

Abstract.

It has been suggested that the activity of Ca²⁺/calmodulin-dependent protein kinase II (CaMKII) increases during acidosis in cardiac muscle. Thus we have investigated the role of CaMKII during acidosis by monitoring intracellular Ca²⁺ (using fura-2) and I _Ca (using the perforated patch clamp technique) during acidosis, in the absence and presence of the CaMKII inhibitor KN-93, in rat isolated ventricular myocytes. In the absence of KN-93, acidosis (pH 6.5) increased the amplitude of the fura-2 transient and prolonged its 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 the 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 during acidosis in the absence of KN-93 but decreased during acidosis in the presence of KN-93. These results suggest that activation of CaMKII during acidosis helps to compensate for the direct inhibitory effects of acidosis on sarcoplasmic reticular Ca²⁺ uptake and I _Ca.