Blocking K+ channels with TEA induces plasmalemma depolarization, increased [Ca2+]i, and ACTH secretion in AtT-20 cells.
Blocking K+ channels induces hormone secretion in various pituitary cell lines by a mechanism which is not completely delineated. In the present study, we employed the mouse pituitary tumor-derived AtT-20 cell as a model to evaluate this phenomenon. We correlated the effect of the K+ channel-blocker, tetraethylammonium (TEA), on K+ current and membrane potential utilizing whole cell recording, on cytosol Ca2+ ([Ca2+]i) concentration utilizing fura-2, and on ACTH secretion utilizing a perifusion system. TEA inhibited voltage-dependent K+ current and initiated membrane depolarization in a dose-dependent fashion. Divergences in the sensitivity to TEA between voltage-dependent K+ currents and membrane depolarization indicate that voltage-dependent K+ channels are not responsible for TEA-induced depolarization TEA (1-30 mM) also induced a concentration-dependent rise in [Ca2+]i concentration and ACTH secretion, both of which were inhibited by removing medium Ca2+. Our data indicate that TEA inhibits K+ currents and induces membrane depolarization; this opens Ca2+ channels in the plasmalemma, causing a rise in [Ca2+]i which initiates ACTH secretion. Alteration of K+ channel permeability by hormones or neurotransmitters may thus play an important regulatory role in controlling pituitary hormone secretion.
Wang
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Department of Physiology, Oregon Health Sciences University, Portland 97201, USA.
Greer
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MA
D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002462:Cell Membrane / Q000502:physiology*; D003600:Cytosol / Q000378:metabolism; D008564:Membrane Potentials; D051379:Mice; D010911:Pituitary Neoplasms / Q000503:physiopathology*; D015221:Potassium Channels / Q000187:drug effects*; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D015221:Potassium Channels; D013757:Tetraethylammonium Compounds; D019789:Tetraethylammonium; D000324:Adrenocorticotropic Hormone; D002118:Calcium