Thyrotropin-releasing hormone stimulates a calcium-activated potassium current in a rat anterior pituitary cell line.
1. The 'giga-seal' patch-electrode technique (Hamill, Marty, Neher, Sakmann & Sigworth, 1981) was used for constant current and voltage-clamp recordings in the GH3 rat anterior pituitary cell line. 2. Thyrotropin-releasing hormone (TRH) causes a membrane hyperpolarization that is mediated by a selective increase in K+ permeability. The hyperpolarization cannot be evoked when the cell is internally perfused with a Ca2+ chelator but persists when the external solution that bathes the cell is Ca2+-free or contains a Ca2+-channel blocker. 3. Under voltage clamp the TRH-induced current is approximately linear at negative potentials (-90 to -30 mV) but markedly enhanced at voltages above -30 mV). Thus, the affected conductance has a voltage-dependent component. 4. The TRH-induced increase in K+ permeability is sensitive to inhibition by 30 mM-TEA and 200 nM-apamin, inhibitors of two distinct Ca2+-activated K+ permeabilities in GH3 cells. 5. The time course of the TRH-induced K+ current is similar to the time course of a TRH-induced transient peak elevation of cytosolic Ca2+ that is due to mobilization of Ca2+ from intracellular stores. 6. The effects of TRH on the K+ current and the rise in cytosolic Ca2+ are half-maximal at 7 nM and 1.7 nM, respectively. 7. It is concluded that the TRH-induced hyperpolarization is mediated by two distinct Ca2+-activated K+ conductances that are activated by release of Ca2+ from an intracellular site.
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D002460:Cell Line; D003600:Cytosol / Q000378:metabolism; D004492:Edetic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D007473:Ion Channels / Q000378:metabolism*; D010903:Pituitary Gland, Anterior / Q000378:metabolism* / Q000502:physiology; D011188:Potassium / Q000378:metabolism*; D051381:Rats; D013268:Stimulation, Chemical; D013973:Thyrotropin-Releasing Hormone / Q000494:pharmacology*
D007473:Ion Channels; C005390:CDTA; D004533:Egtazic Acid; D013973:Thyrotropin-Releasing Hormone; D004492:Edetic Acid; D011188:Potassium; D002118:Calcium