POTENTIATION OF CA2-ACTIVATED SECRETORY ACTIVITY BY A CAMP-MEDIATED MECHANISM IN AVIAN SALT-GLAND CELLS()

In the avian salt gland carbachol (CCh) evokes oscillations in K+ and Cl- current that are sufficient to fully activate secretory activity. Employing the perforated patch-clamp technique, we demonstrate that be ta-adrenergic receptor activation stimulates a sustained adenosine 3', 5'-cyclic monophosphate (cAMP)-dependent Cl- current with no increase in K+ current. This evokes only a modest increase in secretory activit y. However, application of isoproterenol in the presence of a threshol d dose of CCh results in maximal secretory activity. Membrane potentia l measurements demonstrate that isoproterenol stimulates a sustained m embrane depolarization from approximately -45 mV to the Cl- equilibriu m potential (E(Cl)), whereas CCh evokes oscillations in membrane poten tial to levels more negative than E(Cl), representing a mixture of Kand Cl(-)conductances. We conclude that, in agreement with current mod els of fluid secretion, maximal stimulation can only be achieved with simultaneous activation of both K+ and Cl(-)currents. Because isoprote renol fails to stimulate a K+ current, Cl- secretion is reduced as the driving force for Cl(-)secretion is dissipated. However, if a driving force is imposed by increasing K+ channel activity (by coadministerin g CCh), Cl- efflux is sustained. These results could provide a basis f or the marked potentiation of Ca2+-mediated secretion by agonists that increase cAMP seen in in vivo studies of salivary glands and other ex ocrine tissues.