Chronic treatment with D600 enhances development of sodium channels in cultured chick skeletal muscle cells.
We have studied the long-term effects of D600, a blocker of L-type voltage-dependent Ca channels (VDCC), on the development of voltage-dependent Na channels (VDNC) that are sensitive to tetrodotoxin (TTX), by electrophysiological measurements of the maximum rate of rise of the TTX-sensitive Na spike in cultured chick skeletal muscle cells. Chronic treatment with D600 (2-20 microM) caused a dose-dependent increase in the density of VDNC. The density of VDNC was increased by 150-250% when D600 was added to the cultures at 20 microM from the second day of culture onward. Co-treatment with an inhibitor of the transcription of RNA from DNA, alpha-amanitin, or with cycloheximide, an inhibitor of protein synthesis, prevented the up-regulation by D600. Nifedipine, a different type of blocker of L-type VDCC, was also effective in increasing the density of VDNC, and BAY K 8644, an agonist of L-type VDCC, had the opposite effect. It is suggested that the effect of D600 was mediated via a mechanism specific for L-type VDCC that involves regulation of cytosolic levels of Ca2+ and protein synthesis de novo.
Satoh
R
R
Department of Physiology, Kitasato University School of Medicine, Kanagawa, Japan.
Nakabayashi
Y
Y
Kano
M
M
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D002642:Chick Embryo; D004305:Dose-Response Relationship, Drug; D005711:Gallopamil / Q000494:pharmacology*; D009132:Muscles / Q000378:metabolism*; D009543:Nifedipine / Q000494:pharmacology; D015222:Sodium Channels / Q000378:metabolism*; D013997:Time Factors; D015854:Up-Regulation
D015222:Sodium Channels; D005711:Gallopamil; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D009543:Nifedipine