CORTICOTROPIN-RELEASING HORMONE INHIBITS AN INWARDLY RECTIFYING POTASSIUM CURRENT IN RAT CORTICOTROPES

1. The perforated-patch-clamp technique was used to identify an inward ly rectifying K+ current (I-K(IR)) in cultured rat anterior pituitary cells highly enriched in corticotropes. IK(IR) was rapidly activating and highly selective for K+. The K+ conductance was approximately prop ortional to the square root of the extracellular K+ concentration. 2. I-K(IR) was blocked in a voltage-dependent manner by external Ba2+ and Cs+, slightly attenuated by 5 mM 4-aminopyridine (15% inhibition) and insensitive to 10 mM tetra ethylammonium, 2 mM Ca2+, 1 mM Cd2+ and 50 mu M La3+ 3. In physiological saline, 100 mu M Ba2+, which inhibits 8 6 % of I-K(IR)at the cell resting potential, depolarized cells by 6.1 +/- 0.7 mV from a mean resting potential of -59.6 +/- 0.8 mV. 4. Corti cotropin releasing hormone (CRH), which activates adenylyl cyclase and stimulates adrenocorticotropic hormone (ACTH) secretion from corticot ropes, inhibited I-K(IR) by 25% and depolarized the cells by 10.2 +/- 1.0 mV. Dibutyryl cAMP ((Bu)(2)cAMP) mimicked these effects. 5. The me mbrane depolarization evoked by Ba2+ or CRH increased the cell firing frequency. Comparison of cells exhibiting a membrane potential of appr oximately -50 mV revealed that spike frequency in the presence of CRH (109 +/- 7 spikes (5 min)(-1)) was greater than in control(60 +/- 5 sp ikes (5 min)(-1)) or Ba2+-treated (77 +/- 15 spikes (5 min)(-1)) corti cotropes. 6. 6. The data suggest that I-K(IR) contributes to maintenan ce of the resting membrane potential of rat corticotropes. Inhibition of IK(IR) plays a role in, but does not account for all of, the membra ne depolarization and enhancement of firing frequency evoked by CRH.