CORTICOTROPIN-RELEASING HORMONE STIMULATES CA2-TYPE AND P-TYPE CA2+ CHANNELS IN RAT CORTICOTROPES( ENTRY THROUGH L)

CRH induces corticotrope membrane depolarization and facilitates actio n potential firing. The increase in electrical excitability causes lar ge oscillatory increases in cytosolic Ca2+ levels. In this study on hi ghly enriched populations of cultured rat corticotropes, inhibitors we re used to determine the contribution of the Na+ channel and Ca2+ chan nel subtypes to membrane excitability and cytosolic Ca2+ levels. Tetro dotoxin, an inhibitor of the voltage-dependent Na+ channel, inhibited a rapid initial component of the action potential, but generally did n ot influence spontaneous or CRH-induced firing frequency. Tetrodotoxin also had no effect on spontaneous or CRH-induced cytosolic Ca2+ level s. The L-type Ca2+ channel inhibitor nifedipine abolished spontaneous and CRH-induced action potentials and cytosolic Ca2+ transients, but d id not eliminate the CRH-induced membrane depolarization or completely restore cytosolic Ca2+ to basal levels. Inhibition of P-type Ca2+ cha nnels with omega-agatoxin-IVA decreased action potential firing freque ncy and reduced the CRH-induced increase in cytosolic Ca2+. The combin ation of nifedipine and omega-agatoxin-IVA abolished the CRH-induced r ise in Ca2+, but did not abolish the membrane depolarization. Thus, cy tosolic Ca2+ is mainly increased by CRH-induced action potentials that are completely dependent on L-type Ca2+ channels and partially regula ted by P-type Ca2+ channels. CRH-induced Ca2+ entry also occurs indepe ndently of action potentials and is due to P-type, and possibly L-type , Ca2+ channels activated by the CRH-induced membrane depolarization.