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Endocrinology, Vol 136, 3916-3924, Copyright © 1995 by Endocrine Society

ARTICLES

Three high threshold calcium channel subtypes in rat corticotropes

YA Kuryshev, GV Childs and AK Ritchie
Department of Physiology and Biophysics, University of Texas Medical Branch, Galveston 77555-0641, USA.

In this study on highly enriched populations of cultured rat corticotropes, Ca2+ channel inhibitors were used to identify subtypes of the high threshold Ca2+ channel current under voltage clamp conditions. From a holding potential (-50 mV) that eliminated the low threshold T-type current, 52 +/- 4% of the total current in 10 mM Ba2+ was mediated by dihydropyridine-sensitive L-type Ca2+ channels. Blockade of this current was half-maximal at a nifedipine concentration of 187 nM. omega-Agatoxin-IVA (20 nM) maximally inhibited 28 +/- 3% of the total current. This high sensitivity to omega-agatoxin-IVA indicates that this noninactivating current is mediated by P-type Ca2+ channels. A very high threshold, noninactivating current (23 +/- 4% of the total Ba2+ current) remained after maximal inhibition of L- and P- type Ca2+ channels. This current was also resistant to toxins that inhibit N (omega-conotoxin-GVIA)- and Q (omega-conotoxin-MVIIC)-type Ca2+ channels. Because this current had slow activation kinetics and voltage dependence very different from those of the L- and P-type currents in these cells, it was probably mediated by a third unclassified Ca2+ channel subtype (or subtypes). It is concluded that the high threshold current in corticotropes is due to the presence of at least three different Ca2+ channel subtypes.


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