Ca2+/calmodulin-dependent regulation of the density of Na+ channels in embryonic chick skeletal muscle cells during their development in culture.
Regulation of the density of voltage-dependent Na+ channels (VDNC) was studied in chick myotubes during their development in culture. The density of VDNC was assessed quantitatively in terms of the maximum rate of rise (M.R.R.) of Na+ spikes. Chronic treatment of myotubes, whose density of VDNC had reached a plateau level after 6 days in culture, with the calmodulin (CaM) inhibitor W-7 caused a further increase in the density. A derivative of W-7, known as W-5, which has a lower affinity for CaM than does W-7, was without effect. A selective inhibitor of Ca2+/CaM-dependent protein kinase II (CaM-KII), namely, KN-62, also caused an increase in the density of VDNC when its effect was examined in mature myotubes. A structural analogue of KN-62, namely, KN-04, which is a much less effective inhibitor of CaM-KII, was without effect. These results suggest that density of VDNC in developing myotubes is regulated by Ca2+/CaM and CaM-KII. However, the role of CaM-KII in this regulation is not straightforward since it appears to decrease the density of VDNC in mature myotubes, but to increase their density in immature myotubes.
Satoh
R
R
Department of Physiology, Kitasato University School of Medicine, Kanagawa, Japan.
Nakabayashi
Y
Y
Kano
M
M
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives*; D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D002147:Calmodulin / Q000494:pharmacology*; D002478:Cells, Cultured; D002642:Chick Embryo; D004594:Electrophysiology; D007546:Isoquinolines / Q000494:pharmacology; D009132:Muscles / Q000196:embryology* / Q000378:metabolism; D010879:Piperazines / Q000494:pharmacology; D015222:Sodium Channels / Q000187:drug effects / Q000378:metabolism*; D013449:Sulfonamides / Q000494:pharmacology
D002147:Calmodulin; D007546:Isoquinolines; D010879:Piperazines; D015222:Sodium Channels; D013449:Sulfonamides; C063302:KN 62; C017967:W 7; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D002118:Calcium