Abstract

Increased extracellular osmolarity ([Os]e) suppresses stimulated hormone secretion from anterior pituitary cells. Ca2+ influx may mediate this effect. We show that increase in [Os]e (by 18-125%) differentially suppresses L-type and T-type Ca2+ channel currents (IL and IT, respectively); IL was more sensitive than IT. Hyperosmotic suppression of IL depended on the magnitude of increase in [Os]e and was correlated with the percent decrease in pituitary cell volume, suggesting that pituitary cell shrinkage can modulate L-type currents. The hyperosmotic suppression of IL and IT persisted after incubation of pituitary cells either with the actin-disrupter cytochalasin D or with the actin stabilizer phalloidin, suggesting that the actin cytoskeleton is not involved in this modulation. The hyperosmotic suppression of Ca2+ influx was not correlated with changes in reversal potential, membrane capacitance, and access resistance. Together, these results suggest that the hyperosmotic suppression of Ca2+ influx involves Ca2+ channel proteins. We therefore recorded the activity of L-type Ca2+ channels from cell-attached patches while exposing the cell outside the patch pipette to hyperosmotic media. Increased [Os]e reduced the activity of Ca2+ channels but did not change single-channel conductance. This hyperosmotic suppression of Ca2+ currents may therefore contribute to the previously reported hyperosmotic suppression of hormone secretion.