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Corticotropin releasing hormone inhibits an inwardly rectifying potassium current in rat corticotropes
Author(s) -
Kuryshev Yuri A.,
Haak Lee,
Childs Gwen V.,
Ritchie Aileen K.
Publication year - 1997
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1111/j.1469-7793.1997.265bk.x
Subject(s) - corticotropic cell , depolarization , endocrinology , medicine , chemistry , membrane potential , anterior pituitary , adenylyl cyclase , biophysics , patch clamp , resting potential , electrophysiology , biology , hormone , biochemistry , stimulation
1 The perforated‐patch‐clamp technique was used to identify an inwardly rectifying K + current ( I K(IR) ) in cultured rat anterior pituitary cells highly enriched in corticotropes. I K(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 Ba 2+ and Cs + , slightly attenuated by 5 m M 4‐aminopyridine (15% inhibition) and insensitive to 10 m M tetra‐ethylammonium, 2 m M Ca 2+ , 1 m M Cd 2+ and 50 μ M La 3+ . 3 In physiological saline, 100 μ M Ba 2+ , which inhibits 86% 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 Corticotropin releasing hormone (CRH), which activates adenylyl cyclase and stimulates adrenocorticotropic hormone (ACTH) secretion from corticotropes, 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 membrane depolarization evoked by Ba 2+ 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 I K(IR) contributes to maintenance of the resting membrane potential of rat corticotropes. Inhibition of I K(IR) plays a role in, but does not account for all of, the membrane depolarization and enhancement of firing frequency evoked by CRH.