LONG-TERM REGULATION OF CALCIUM CHANNELS IN CLONAL PITUITARY-CELLS BYEPIDERMAL GROWTH-FACTOR, INSULIN, AND GLUCOCORTICOIDS

In rat pituitary GH(3) cells, epidermal growth factor (EGF) and insuli n stimulate prolactin production, whereas glucocorticoids exert the op posite effect. In the present study, GH(3) cells were subjected to who le-cell patch clamp to assess the chronic actions of such regulatory f actors on voltage-dependent calcium currents. Before the electrical re cording, cells were grown 5-6 d either under standard conditions or in the presence of 5 nM EGF, 100 nM insulin, 1 mu M dexamethasone or 5 m u M cortisol. EGF induced a twofold selective increase in high-thresho ld calcium current density. Insulin and glucocorticoids, on the other hand, specifically regulated lo iu-threshold Ca channels. Current dens ity through these channels increased by 70% in insulin-treated cells, and decreased by 50% in cells exposed to dexamethasone or cortisol. Ot her Ca channel properties investigated (conductance-voltage curves, de activation rates, time course and voltage dependence of low-threshold current inactivation) were unaffected by the chemical messengers. The alterations in current density persisted for many hours after removing the regula tory factors from the culture medium. In fact, the stimula tory action of EGF high-threshold current lasted > 3 d. The results su ggest that the control of prolactin production by the factors tested i nvokes regulation of the surface density of functional Ca channels in the plasma membrane.