Potentiation of Ca(2+)-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 beta-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 activity. However, application of isoproterenol in the presence of a threshold dose of CCh results in maximal secretory activity. Membrane potential measurements demonstrate that isoproterenol stimulates a sustained membrane depolarization from approximately -45 mV to the Cl- equilibrium potential (ECl), whereas CCh evokes oscillations in membrane potential to levels more negative than ECl, representing a mixture of K+ and Cl- conductances. We conclude that, in agreement with current models of fluid secretion, maximal stimulation can only be achieved with simultaneous activation of both K+ and Cl- currents. Because isoproterenol 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 coadministering CCh), Cl- efflux is sustained. These results could provide a basis for the marked potentiation of Ca(2+)-mediated secretion by agonists that increase cAMP seen in in vivo studies of salivary glands and other exocrine tissues.
Martin
S C
SC
Department of Physiology, University of Rochester School of Medicine and Dentistry, New York 14642.
Thompson
J
J
Shuttleworth
T J
TJ
D000818:Animals; D002118:Calcium / Q000502:physiology*; D002217:Carbachol / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology*; D004372:Ducks; D004553:Electric Conductivity; D004594:Electrophysiology; D007545:Isoproterenol / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D012491:Salt Gland / Q000166:cytology / Q000378:metabolism* / Q000502:physiology*; D015290:Second Messenger Systems
D002217:Carbachol; D000242:Cyclic AMP; D007545:Isoproterenol; D002118:Calcium