ACTIONS OF GROWTH-HORMONE-RELEASING HORMONE ON RAT PITUITARY-CELLS - INTRACELLULAR CALCIUM AND IONIC CURRENTS

Actions of growth-hormone-releasing hormone (GHRH) on single rat anter ior pituitary cells were studied using indo-1 fluorescence to monitor changes in intracellular calcium, [Ca2+]i, and perforated-patch record ing to measure changes in membrane potential and ionic currents. GHRH elevated [Ca2+]i in non-voltage-clamped cells by a mechanism that was dependent upon extracellular Na+ and Ca2+ and was blocked by the dihyd ropyridine Ca2+-channel blocker, nitrendipine. Resting cells had a flu ctuating membrane potential whose a mean value depolarized by 9 mV in response to GHRH. The membrane-permeant cAMP analogue, 8-(4-chlorophen ylthio)cAMP, mimicked the action of GHRH on membrane potential. Under voltage clamping, GHRH activated a small inward current (1-5 pA). Two types of response could be distinguished. The type I response had an i nward current that was largest at more negative potentials (-90 mV), a nd the type II response had inward current that was larger at more pos itive potentials (-40 to -70 mV). Both types of response were reversib le and blocked by removal of extracellular Na+. These results suggest that the rise in [Ca2+],produced by GHRH in non-voltage-clamped cells results from the activation via cAMP of a Na+-dependent conductance, w hich depolarizes the cell and increases the Ca2+ influx through voltag e-gated Ca2+ channels.