Na diffusion dependent Ca handling in rabbit ventricular myocytes

Intracellular Na concentration ([Na]_i) plays a pivotal role in modulating the electrical and contractile activity of the heart via the Na/Ca and Na/H exchange mechanisms. Several studies showed that important [Na]_i gradients exist close to the cell membrane. Thus, intracellular Na diffusion has to be slow with respect to the rates of Na transport across the sarcolemma. Here we extended the rabbit ventricular action potential and Ca transient model developed in our laboratory to establish [Na]_i gradients that have been inferred directly from experimental data. In our simulations, a dramatic slowing of the Na diffusion coefficient or higher than expected colocalization between Na and Ca transporters is required to predict experimentally derived indirect effects of altered local [Na]_i on Ca handling. The results suggest some directions for further laboratory investigation and modeling.