title: Negative modulation of sodium channels in cultured chick muscle cells by the channel activator batrachotoxin.
abstract: We have investigated the possibility that cellular control of membrane excitability involves feedback mechanisms in which the degree of activity of voltage-sensitive Na+ channels regulates the number of these channels. Using two independent assays, channel-mediated Na+ uptake and the specific binding of [3H] saxitoxin, we have studied the effects of pharmacological activation of Na+ channels with batrachotoxin (BTX) on the number and properties of these channels. Upon exposure of cultured muscle cells to BTX (1 microM), the number of surface Na+ channels decreases by approximately 75%, with a half-time of 3-6 h. This decrease is prevented by pharmacological blockade of these channels and does not reflect changes in the apparent affinities towards either BTX or saxitoxin. This reduction is reversible: a gradual increase in surface Na+ channels that is dependent on protein synthesis is observed upon removal of the activator. The BTX-induced decrease in Na+ channels is associated with an enhanced rate of disappearance of surface Na+ channels. These findings point to the existence of a down-regulation mechanism for the modulation of membrane excitability under conditions of elevated Na+ channel activity.
authors.forename: D
authors.initials: D
authors.lastname: Bar-Sagi
authors.forename: J
authors.initials: J
authors.lastname: Prives
mesh_terms: D000818:Animals; D001496:Batrachotoxins / Q000494:pharmacology*; D002478:Cells, Cultured; D002642:Chick Embryo; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism*; D009132:Muscles / Q000378:metabolism*; D012530:Saxitoxin / Q000378:metabolism; D012604:Scorpion Venoms / Q000494:pharmacology; D012964:Sodium / Q000378:metabolism*; D013997:Time Factors
chemical_list: D001496:Batrachotoxins; D007473:Ion Channels; D012604:Scorpion Venoms; D012530:Saxitoxin; D012964:Sodium