Characterization of an M-like current modulated by thyrotropin-releasing hormone in normal rat lactotrophs.
In rat pituitary lactotrophs, a component of thyrotropin-releasing hormone (TRH)-induced prolactin secretion is dependent on extracellular calcium and is associated with an increase in action-potential firing. The mechanism underlying the TRH-induced increase in firing frequency was investigated using the perforated-patch variation of the whole-cell patch-clamp technique. TRH was found to inhibit a voltage-dependent, noninactivating K+ current that was similar to M-currents originally identified in neurons. The TRH-modulated M-like current started to activate at approximately -60 mV and had a V0 of -28 mV and thus would be active under the normal resting potentials of lactotrophs (-35 to -45 mV). Exponential fits to deactivating tail currents revealed a fast and a slow component. The deactivation rates of the M-like current and the ratio of the fast to the slow component of deactivation were found to increase with more hyperpolarized potentials. In addition, increasing the duration of command potentials led to the conversion of the fast component to the slow component of deactivation. The M-like current in lactotrophs was partially sensitive to 4-aminopyridine and tetraethylammonium. TRH inhibition of this current was associated with acceleration of deactivation rates and a depolarizing shift in the voltage of activation (V0 = -17 mV). The effect of TRH on the M-like current was lost in whole-cell voltage-clamp conditions, suggesting the requirement of an important cytosolic component that mediates the effect of TRH.
Sankaranarayanan
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Department of Veterinary Comparative Anatomy, College of Veterinary Medicine, Washington State University, Pullman 99164-6520, USA.
Simasko
S M
SM
D000200:Action Potentials; D000818:Animals; D002118:Calcium / Q000502:physiology; D004553:Electric Conductivity; D005260:Female; D008564:Membrane Potentials; D010903:Pituitary Gland, Anterior / Q000166:cytology / Q000502:physiology*; D011188:Potassium / Q000502:physiology; D011388:Prolactin / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology; D013973:Thyrotropin-Releasing Hormone / Q000494:pharmacology / Q000502:physiology*
D013757:Tetraethylammonium Compounds; D013973:Thyrotropin-Releasing Hormone; D019789:Tetraethylammonium; D011388:Prolactin; D011188:Potassium; D002118:Calcium