Spatial Regulation of Intracellular pH in the Ventricular Myocyte

In the cardiac myocyte, an adequate intracellular proton mobility is necessary for coupling sarcolemmal proton transport to bulk cytoplasm during intracellular pH regulation. It is also important for dissipating intracellular pH nonuniformity in response to local acid/base disturbances. Because cardiac myocytes have a high buffering capacity, intracellular H(+) mobility is low. Spatial H(i)+ movements occur via a mobile buffer shuttle that most likely involves intracellular dipeptides. In the present work with isolated ventricular myocytes, it is demonstrated that stimulating a large acid efflux on sarcolemmal Na(+)-H(+) exchange, results in spatial pH(i) gradients of up to 0.1 U. These may have important implications for pH-sensitive processes within the cell, such as contraction. By using computational modeling, it is shown that the gradients can be attributed to the low H(i)+ mobility. Computational modeling is also used to assess the importance of H(i)+ mobility in mediating local recovery of pH following an acidosis in a small region of the cell. Results indicate that local mechanisms for H(i)+ movement will be important in determining the global regulation of intracellular pH.