Reduced calcium current density in female versus male mouse adrenal chromaffin cells in situ

Neuroendocrine adrenal medullary chromaffin cells are a main output of the sympathetic nervous system. Acute stress activates the sympatho-adrenal stress reflex, excites adrenal chromaffin cells, and elicits catecholamine secretion into the circulation. Previous studies have demonstrated that stress-evoked serum catecholamine levels are greater in males. We investigated potential mechanistic bases for this gender dimorphism at the level of the adrenal medulla. We utilized in situ single-cell perforated patch voltage clamp to measure basic electrophysiological parameters that affect cell excitability. We found that chromaffin cells from male and female mice exhibit statistically identical depolarization-evoked calcium currents. However, the resting capacitance, an index of cell surface area, was significantly higher in cells from female mice. Thus the current density in female cells was significantly lower. We found that inhibition of protein kinase C, an enzyme shown to regulate both exocytosis and endocytosis, eliminates the cell surface area gender dimorphism. Finally, we performed kinetic simulations of the secretion process and report a predicted elevated secretory capacity in male cells. Thus, regulation of cell size may act to decrease cell excitability in female cells and may in-part represent the mechanistic basis for increased stress-evoked catecholamine secretion described in males.