Na/Ca Exchange in Function, Growth, and Demise of ?-Cells
Recent knowledge concerning the Na/Ca exchanger (NCX) in the pancreatic ?-cell is reviewed. The ?-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 ?-cell, the exchanger displays a high capacity, accounts for about 70% of Ca2+ extrusion, and participates in Ca2+ inflow during membrane depolarization. In the mouse, however, the contribution of the exchanger to Ca2+ extrusion is more modest, and to Ca2+ inflow, less evident. The exchanger has a stoichiometry of 3 Na+ for 1 Ca2+, is electrogenic, and displays a reversal potential at ?20 mV. Although being of low magnitude, the current generated by the exchanger shapes glucose-induced ?-cell electrical activity and intracellular Ca2+ oscillations. Intracellular Ca2+ may also trigger apoptosis. For instance, overexpression of the exchanger increases Ca2+-dependent and Ca2+-independent ?-cell death by apoptosis, a phenomenon resulting from the depletion of ER Ca2+ stores with subsequent activation of caspase-12. Na/Ca exchange overexpression also reduces ?-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 ?-cell.
na/ca exchange pancreatic ?-cell ca2+ oscillations apoptosis caspase-12 endoplasmic reticulum stress