Sodium fluoride produces a K+ efflux by increasing intracellular Ca2+ through Na+-Ca2+ exchange.
Acute fluoride intoxication increases intracellular calcium (Cai), manifested by increased twitch tension in cardiac muscle, and by potassium efflux (mediated by Ca2+-dependent K+ channels) in fluoridated erythrocytes. Fluoride, like isoproterenol, stimulates adenylate cyclase, and could increase Cai via the effects of cAMP on Ca2+ channels. However, while the inotropic effects of fluoride mimicked isoproterenol in rat atria, their effects on the time course of isometric contraction were quite different. In addition, acetylcholine negated isoproterenol's effect on twitch tension but did not modulate the effects of fluoride. Further, the Ca2+ channel antagonist verapamil had no effect on fluoride-stimulated K+ efflux from erythrocytes. Fluoride also inhibits Na+-K+ ATPase, and increases intracellular Na+, so could increase Cai via Na+-Ca2+ exchange. Lanthanum, which blocks Na+-Ca2+ exchange, blocks fluoride-induced K+ efflux in erythrocytes. We conclude that the effects of fluoride on adenylate cyclase are not important in intact tissue, and that inhibition of Na+-K+ ATPase and subsequent Na2+-Ca2+ exchange may be the mechanism of increased Cai in acute fluoride toxicity.
McIvor
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ME
Cummings
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CC
D000818:Animals; D002118:Calcium / Q000378:metabolism; D004912:Erythrocytes / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D006947:Hyperkalemia / Q000139:chemically induced; D066298:In Vitro Techniques; D007474:Ion Exchange; D007545:Isoproterenol / Q000494:pharmacology; D007811:Lanthanum; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D010042:Ouabain / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012969:Sodium Fluoride / Q000633:toxicity*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
D010042:Ouabain; D007811:Lanthanum; D012969:Sodium Fluoride; D000254:Sodium-Potassium-Exchanging ATPase; D007545:Isoproterenol; D011188:Potassium; D002118:Calcium