Target size analysis of skeletal muscle Ca2+ channels. Positive allosteric heterotropic regulation by d-cis-diltiazem is associated with apparent channel oligomer dissociation.
[3H]PN 200-110, a potent chiral benzoxadiazol 1,4-dihydropyridine Ca2+ antagonist was used to label guinea pig skeletal muscle Ca2+ channels. [3H]PN 200-110 binds with a Kd of approximately 1 nM to a homogeneous population of non-interacting binding sites; d-cis-diltiazem, but not l-cis-diltiazem increases the Bmax of [3H]PN 200-110 by 25% and slows the dissociation rate 3-fold at 37 degrees C. Target size analysis of the [3H]PN 200-110-labelled Ca2+ channels with 10 MeV electrons gave an Mr of 136 000 which was reduced to 75 000 by d-cis-diltiazem treatment of membranes. It is concluded that positive heterotropic allosteric regulation by d-cis-diltiazem is accompanied by channel oligomer dissociation.
D000494:Allosteric Regulation / Q000187:drug effects; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology*; D001665:Binding Sites; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers; D004110:Diltiazem / Q000494:pharmacology*; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism*; D017275:Isradipine; D008297:Male; D009132:Muscles / Q000378:metabolism*; D010069:Oxadiazoles; D013237:Stereoisomerism
D001552:Benzazepines; D002121:Calcium Channel Blockers; D007473:Ion Channels; D010069:Oxadiazoles; D004110:Diltiazem; D002118:Calcium; D017275:Isradipine