Inhibition of membrane currents and rises of intracellular Ca2+ in PC12 cells by CGS 9343B, a calmodulin inhibitor.
The calmodulin inhibitor 1,3-dihydro-1-[1-((4-methyl-4H,6H-pyrrolo[1,2-a]-[4,1]benzoxazepin - 4-yl)methyl)-4-piperidinyl]-2H-benzimidazol-2-one maleate (CGS 9343B) caused a reversible block of voltage-activated Ca2+, Na+, and K+ currents in differentiated rat pheochromocytoma (PC12) cells. The drug also inhibited nicotinic acetylcholine receptor (nAChR) channel currents but not inward currents evoked by extracellular ATP. Depolarization-induced intracellular Ca2+ transients were almost completely inhibited in growth cones and cell bodies by CGS 9343B. Our results suggest actions of CGS 9343B on ion fluxes unrelated to calmodulin inhibition.
Neuhaus
R
R
Department of Pharmacology, University of Bern, Switzerland.
Reber
B F
BF
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002147:Calmodulin / Q000037:antagonists & inhibitors*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D018680:Cholinergic Antagonists; D004594:Electrophysiology; D007473:Ion Channels / Q000187:drug effects*; D016716:PC12 Cells; D015221:Potassium Channels / Q000187:drug effects; D051381:Rats; D015222:Sodium Channels / Q000187:drug effects
D001562:Benzimidazoles; D002121:Calcium Channel Blockers; D002147:Calmodulin; D018680:Cholinergic Antagonists; D007473:Ion Channels; D015221:Potassium Channels; D015222:Sodium Channels; C052087:CGS 9343B; D000255:Adenosine Triphosphate; D002118:Calcium