title: Acute modulation of adrenal chromaffin cell BK channel gating and cell excitability by glucocorticoids.
abstract: Although adrenal glucocorticoids cortisol and corticosterone (CORT) have numerous "genomic" effects on adrenomedullary chromaffin cells, acute modulatory actions remain largely unknown, despite rapid stress-related changes in secretion. We report that 1 microM glucocorticoids rapidly modulate gating of chromaffin cell BK channels and action potential firing. In general, CORT, or the analog dexamethasone (DEX), increased channel activity in inside-out bovine patches, an effect not blocked by the glucocorticoid receptor (GR) antagonist RU38486. By contrast, these steroids could profoundly inhibit BK activation in many rat patches, while facilitating activation in others. We show that BK inhibition arises from a negative shift in the voltage dependence of BK inactivation paralleling that for activation. We report that rat cells characteristically exhibit greater repetitive firing ability than bovine cells in the absence of glucocorticoids. In both species, steroid application typically increased firing responses to smaller current injections, attributable to BK-enhanced repolarization and Na+ channel deinactivation. However, in rat cells, where BK inactivation is generally faster and more complete, glucocorticoids tended to dampen responses to stronger stimuli. Thus, in the context of natural variation in BK gating, glucocorticoids can either promote or limit firing responses. We suggest that steroids exploit BK gating variety to tailor catecholamine output in a species- and context-specific fashion.
authors.affiliation: Department of Neurobiology and Behavior, Cornell University, Ithaca, New York 14853, USA.
authors.forename: Peter V
authors.initials: PV
authors.lastname: Lovell
authors.forename: Jonathan T
authors.initials: JT
authors.lastname: King
authors.forename: David P
authors.initials: DP
authors.lastname: McCobb
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002417:Cattle; D002478:Cells, Cultured; D019439:Chromaffin Cells / Q000187:drug effects* / Q000502:physiology; D003907:Dexamethasone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004558:Electric Stimulation; D005938:Glucocorticoids / Q000494:pharmacology*; D006727:Hormone Antagonists / Q000494:pharmacology; D051036:Large-Conductance Calcium-Activated Potassium Channels; D008564:Membrane Potentials / Q000187:drug effects; D015735:Mifepristone / Q000494:pharmacology; D009433:Neural Inhibition / Q000187:drug effects; D018408:Patch-Clamp Techniques / Q000379:methods; D011188:Potassium / Q000378:metabolism; D024681:Potassium Channels, Calcium-Activated / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D013045:Species Specificity
chemical_list: D005938:Glucocorticoids; D006727:Hormone Antagonists; D051036:Large-Conductance Calcium-Activated Potassium Channels; D024681:Potassium Channels, Calcium-Activated; D015735:Mifepristone; D003907:Dexamethasone; D011188:Potassium; D002118:Calcium