title: Electrical activity and cytosolic calcium regulate levels of tetrodotoxin-sensitive sodium channels in cultured rat muscle cells.
abstract: Pharmacological blockade of the spontaneous electrical activity present in primary cultures of rat myotubes by growth in bupivacaine, tetrodotoxin, or KCl was found to increase the number of voltage-sensitive Na+ channels 38-83% as measured by the specific binding of [3H]saxitoxin. The inhibition of spontaneous electrical activity and increase in channel density by bupivacaine displayed an identical dose response, with a half-maximal effect at 3.0 microM. Growth of myotubes in the presence of 1 microM A23187, a Ca2+-specific ionophore, resulted in a 30-60% decrease in the number of tetrodotoxin-sensitive channels with no change in affinity for [3H]saxitoxin. A23187 was able to overcome the increase in channel density produced by bupivacaine. These results suggest the presence of a Ca2+-mediated negative feedback system in which electrical excitability may be regulated by altering the number of tetrodotoxin-sensitive Na+ channels.
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D005333:Fetus; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D009119:Muscle Contraction; D009132:Muscles / Q000502:physiology*; D051381:Rats; D012964:Sodium / Q000378:metabolism*; D013779:Tetrodotoxin / Q000494:pharmacology*
chemical_list: D007473:Ion Channels; D013779:Tetrodotoxin; D012964:Sodium; D002118:Calcium