title: Corticotropin-releasing hormone stimulates Ca2+ entry through L- and P-type Ca2+ channels in rat corticotropes.
abstract: CRH induces corticotrope membrane depolarization and facilitates action potential firing. The increase in electrical excitability causes large oscillatory increases in cytosolic Ca2+ levels. In this study on highly enriched populations of cultured rat corticotropes, inhibitors were used to determine the contribution of the Na+ channel and Ca2+ channel subtypes to membrane excitability and cytosolic Ca2+ levels. Tetrodotoxin, an inhibitor of the voltage-dependent Na+ channel, inhibited a rapid initial component of the action potential, but generally did not influence spontaneous or CRH-induced firing frequency. Tetrodotoxin also had no effect on spontaneous or CRH-induced cytosolic Ca2+ levels. The L-type Ca2+ channel inhibitor nifedipine abolished spontaneous and CRH-induced action potentials and cytosolic Ca2+ transients, but did not eliminate the CRH-induced membrane depolarization or completely restore cytosolic Ca2+ to basal levels. Inhibition of P-type Ca2+ channels with omega-agatoxin-IVA decreased action potential firing frequency and reduced the CRH-induced increase in cytosolic Ca2+. The combination of nifedipine and omega-agatoxin-IVA abolished the CRH-induced rise in Ca2+, but did not abolish the membrane depolarization. Thus, cytosolic Ca2+ is mainly increased by CRH-induced action potentials that are completely dependent on L-type Ca2+ channels and partially regulated by P-type Ca2+ channels. CRH-induced Ca2+ entry also occurs independently of action potentials and is due to P-type, and possibly L-type, Ca2+ channels activated by the CRH-induced membrane depolarization.
authors.affiliation: Department of Physiology and Biophysics, University of Texas Medical Branch, Galveston 77555, USA.
authors.forename: Y A
authors.initials: YA
authors.lastname: Kuryshev
authors.forename: G V
authors.initials: GV
authors.lastname: Childs
authors.forename: A K
authors.initials: AK
authors.lastname: Ritchie
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002104:Cadmium / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000502:physiology*; D002478:Cells, Cultured; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology*; D003600:Cytosol / Q000378:metabolism; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009543:Nifedipine / Q000494:pharmacology; D010903:Pituitary Gland, Anterior / Q000502:physiology*; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015222:Sodium Channels / Q000502:physiology; D013111:Spider Venoms / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D020867:omega-Agatoxin IVA
chemical_list: D002121:Calcium Channel Blockers; D015220:Calcium Channels; D015222:Sodium Channels; D013111:Spider Venoms; D020867:omega-Agatoxin IVA; D002104:Cadmium; D013779:Tetrodotoxin; D003994:Bucladesine; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D009543:Nifedipine; D011188:Potassium; D002118:Calcium