Membrane potential changes of mouse adrenal zona fasciculata cells in response to adrenocorticotropin and adenosine 3',5'-monophosphate.
ACTH superfused onto mouse adrenal zona fasciculata tissue caused a transient, dose-dependent membrane depolarization. The log of the dose of ACTH was linearly related to the magnitude of depolarization. The onset of depolarization was rapid and dose dependent. Resting membrane potential changes observed after ACTH were blocked by CoCl2 but not tetrodotoxin or 4-aminopyridine, indicating that these depolarizations were dependent primarily on transmembrane Ca++ flux. CoCl2 also significantly blocked ACTH-stimulated adrenal steroid production; 4-aminopyridine had a much smaller and greatly delayed effect, whereas tetrodotoxin had no detectable effect on steroidogenesis. cAMP administration to adrenal zona fasciculata cells elicited transient, dose-dependent membrane depolarizations, which closely resembled those observed after ACTH treatment. In contrast to ACTH, CoCl2 did not block the cAMP-induced depolarization. These and other studies indicate that ACTH initiates a complex series of events by which steroidogenesis is stimulated. One mechanism may involve a change in membrane permeability to Ca++ independently of cAMP generation; a second mechanism may involve the activation of adenylate cyclase which subsequently influences the membrane conductance of the fasciculata cell membrane.
D015761:4-Aminopyridine; D000305:Adrenal Cortex Hormones / Q000378:metabolism; D000311:Adrenal Glands / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology*; D000631:Aminopyridines / Q000494:pharmacology; D000818:Animals; D003035:Cobalt / Q000494:pharmacology; D000242:Cyclic AMP / Q000494:pharmacology*; D007473:Ion Channels / Q000187:drug effects; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D013779:Tetrodotoxin / Q000494:pharmacology
D000305:Adrenal Cortex Hormones; D000631:Aminopyridines; D007473:Ion Channels; D003035:Cobalt; D013779:Tetrodotoxin; D000324:Adrenocorticotropic Hormone; D015761:4-Aminopyridine; D000242:Cyclic AMP