Three high threshold calcium channel subtypes in rat corticotropes.
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.
Kuryshev
Y A
YA
Department of Physiology and Biophysics, University of Texas Medical Branch, Galveston 77555-0641, USA.
Childs
G V
GV
Ritchie
A K
AK
D000818:Animals; D001464:Barium / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000032:analysis* / Q000145:classification* / Q000187:drug effects; D002462:Cell Membrane / Q000502:physiology / Q000648:ultrastructure; D002478:Cells, Cultured; D004095:Dihydropyridines / Q000494:pharmacology; D004594:Electrophysiology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D010455:Peptides / Q000494:pharmacology; D010903:Pituitary Gland, Anterior / Q000737:chemistry* / Q000166:cytology* / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley; D013111:Spider Venoms / Q000494:pharmacology; D013997:Time Factors; D020867:omega-Agatoxin IVA; D020960:omega-Conotoxins
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D004095:Dihydropyridines; D010455:Peptides; D013111:Spider Venoms; D020867:omega-Agatoxin IVA; D020960:omega-Conotoxins; C075851:omega-conotoxin-MVIIC; D001464:Barium