Corticotropin releasing hormone inhibits an inwardly rectifying potassium current in rat corticotropes.
1. The perforated-patch-clamp technique was used to identify an inwardly rectifying K+ current (IK(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 proportional to the square root of the extracellular K+ concentration. 2. IK(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 tetraethylammonium, 2 mM Ca2+, 1 mM Cd2+ and 50 microM La3+. 3. In physiological saline, 100 microM Ba2+, which inhibits 86% of IK(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. Corticotropin releasing hormone (CRH), which activates adenylyl cyclase and stimulates adrenocorticotropic hormone (ACTH) secretion from corticotropes, inhibited IK(IR) by 25% and depolarized the cells by 10.2 +/- 1.0 mV. Dibutyryl cAMP ((Bu)2cAMP) mimicked these effects. 5. The membrane depolarization evoked by Ba2+ or CRH increased the cell firing frequency. Comparison of cells exhibiting a membrane potential of approximately -50 mV revealed that spike frequency in the presence of CRH (109 +/- 7 spikes (5 min)-1) was greater than in control (60 +/- 5 spikes (5 min)-1) or Ba(2+)-treated (77 +/- 15 spikes (5 min)-1) corticotropes. 6. The data suggest that IK(IR) contributes to maintenance of the resting membrane potential of rat corticotropes. Inhibition of IK(IR) plays a role in, but does not account for all of, the membrane depolarization and enhancement of firing frequency evoked by CRH.
Kuryshev
Y A
YA
Department of Physiology and Biophysics, University of Texas Medical Branch, Galveston 77555, USA.
Haak
L
L
Childs
G V
GV
Ritchie
A K
AK
D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D001464:Barium / Q000494:pharmacology; D002104:Cadmium / Q000494:pharmacology; D002478:Cells, Cultured; D002586:Cesium / Q000494:pharmacology; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology*; D005071:Evoked Potentials / Q000187:drug effects / Q000502:physiology; D007811:Lanthanum / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D010903:Pituitary Gland, Anterior / Q000187:drug effects / Q000502:physiology*; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000502:physiology; D024661:Potassium Channels, Inwardly Rectifying; D051381:Rats; D017207:Rats, Sprague-Dawley; D012044:Regression Analysis; D012964:Sodium / Q000494:pharmacology; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology
D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D013757:Tetraethylammonium Compounds; D002104:Cadmium; D002586:Cesium; D001464:Barium; D019789:Tetraethylammonium; D007811:Lanthanum; D003346:Corticotropin-Releasing Hormone; D012964:Sodium; D015761:4-Aminopyridine