Negative modulation of sodium channels in cultured chick muscle cells by the channel activator batrachotoxin.
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.
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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
D001496:Batrachotoxins; D007473:Ion Channels; D012604:Scorpion Venoms; D012530:Saxitoxin; D012964:Sodium