Na/Ca exchange in function, growth, and demise of beta-cells

Recent knowledge concerning the Na/Ca exchanger (NCX) in the pancreatic beta-cell is reviewed. The beta-cell expresses various NCX1 splice variants in a species-specific pattern (NCX1.3 and 1.7 in the rat; NCX1.2, 1.3, and 1.7 in the mouse) and in variable and different proportions. In the rat beta-cell, the exchanger displays a high capacity, accounts for about 70% of Ca(2+) extrusion, and participates in Ca(2+) inflow during membrane depolarization. In the mouse, however, the contribution of the exchanger to Ca(2+) extrusion is more modest, and to Ca(2+) inflow, less evident. The exchanger has a stoichiometry of 3 Na(+) for 1 Ca(2+), is electrogenic, and displays a reversal potential at -20 mV. Although being of low magnitude, the current generated by the exchanger shapes glucose-induced beta-cell electrical activity and intracellular Ca(2+) oscillations. Intracellular Ca(2+) may also trigger apoptosis. For instance, overexpression of the exchanger increases Ca(2+)-dependent and Ca(2+)-independent beta-cell death by apoptosis, a phenomenon resulting from the depletion of ER Ca(2+) stores with subsequent activation of caspase-12. Na/Ca exchange overexpression also reduces beta-cell growth. Hence, the Na/Ca exchanger is a versatile system that appears to play an important role in the function, growth, and demise of the beta-cell.