Inhibition of membrane currents and rises of intracellular Ca2+ in PC12 cells by CGS 9343B, a calmodulin inhibitor.

Abstract

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.

• Authors: R Neuhaus, B F Reber
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 226 Issue 2 Pg. 183-5 (Jun 05 1992) ISSN: 0014-2999 [Print] Netherlands
• PMID: 1379190 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Benzimidazoles
• Calcium Channel Blockers
• Calmodulin
• Cholinergic Antagonists
• Ion Channels
• Potassium Channels
• Sodium Channels
• CGS 9343B
• Adenosine Triphosphate
• Calcium

Topics

• Adenosine Triphosphate (metabolism)
• Animals
• Benzimidazoles (pharmacology)
• Calcium (metabolism)
• Calcium Channel Blockers (pharmacology)
• Calmodulin (antagonists & inhibitors)
• Cell Membrane (drug effects, metabolism)
• Cholinergic Antagonists
• Electrophysiology
• Ion Channels (drug effects)
• PC12 Cells
• Potassium Channels (drug effects)
• Rats
• Sodium Channels (drug effects)