Anticalmodulin drugs block the sodium gating current of squid giant axons.
The effects of calmodulin (CaM) antagonists (W-7, W-5, trifluoperazine, chlorpromazine, quinacrine, diazepam, propericyazine and carmidazolium) on the sodium and potassium channels were studied on the intracellularly perfused and voltage-clamped giant axon of the squid. It was found that the drugs are more potent blockers of the sodium current than of the potassium current. The drugs also reduce the sodium gating current. The blockage of the sodium and gating current can be explained by assuming that the drugs interact with the sodium gating subunit in one of its closed states. The site of action is probably the intracellular surface of the axolemma where presumably a Ca(2+)-calmodulin complex can be formed.
Ichikawa
M
M
Electrotechnical Laboratory, Molecular and Cellular Neuroscience Section, Ibaraki, Japan.
Urayama
M
M
Matsumoto
G
G
D000818:Animals; D001369:Axons / Q000187:drug effects / Q000378:metabolism*; D001693:Biological Transport, Active / Q000187:drug effects; D002147:Calmodulin / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D002746:Chlorpromazine / Q000494:pharmacology; D049832:Decapodiformes; D003975:Diazepam / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D015640:Ion Channel Gating / Q000187:drug effects*; D008564:Membrane Potentials / Q000187:drug effects; D010640:Phenothiazines / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism*; D011796:Quinacrine / Q000494:pharmacology; D012964:Sodium / Q000378:metabolism*; D013449:Sulfonamides / Q000494:pharmacology; D014268:Trifluoperazine / Q000494:pharmacology
D002147:Calmodulin; D007093:Imidazoles; D010640:Phenothiazines; D013449:Sulfonamides; D014268:Trifluoperazine; C031938:calmidazolium; C017967:W 7; C034700:N-(6-aminohexyl)-1-naphthalenesulfonamide; D012964:Sodium; D011796:Quinacrine; D003975:Diazepam; D011188:Potassium; D002746:Chlorpromazine