Acute reduction of extracellular sodium differentially affects receptor-mediated and K+-induced calcium uptake in PC12 pheochromocytoma cells.

Using a rapid-quench method to measure 45Ca2+ uptake into PC12 cells in suspension, we have studied basal, carbachol-stimulated and K+-induced Ca2+ uptake under control conditions [( Na+]o = 130 mM) and in the presence of acutely lowered extracellular sodium concentration [( Na+]o = 65 mM). Acute reduction of [Na+]o stimulates basal and K+-evoked Ca2+ uptake, but reduces net carbachol-stimulated uptake. Since total Ca2+ uptake measured in the presence of carbachol under control and low [Na+]o conditions is unchanged, the reduction in carbachol-stimulated uptake is due to the increase in basal uptake induced by low [Na+]o. These results reconcile apparently conflicting data regarding a specific Na+ requirement for nicotinic acetylcholine receptor-mediated responses in PC12 cells and adrenal chromaffin cells and suggest a mechanism for loss of nicotinic acetylcholine receptor (nAChR) responsiveness to agonists under low Na+ conditions.