McIvor M E, Cummings C C
Toxicol Lett. 1987 Sep;38(1-2):169-76. doi: 10.1016/0378-4274(87)90125-1.
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.
急性氟中毒会增加细胞内钙（Cai），表现为心肌抽搐张力增加，以及氟化红细胞中的钾外流（由钙依赖性钾通道介导）。氟化物与异丙肾上腺素一样，会刺激腺苷酸环化酶，并可能通过环磷酸腺苷（cAMP）对钙通道的作用来增加Cai。然而，虽然氟化物在大鼠心房中的变力作用模拟了异丙肾上腺素，但其对等长收缩时间进程的影响却大不相同。此外，乙酰胆碱可消除异丙肾上腺素对抽搐张力的影响，但不调节氟化物的作用。此外，钙通道拮抗剂维拉帕米对氟化物刺激的红细胞钾外流没有影响。氟化物还会抑制钠钾ATP酶，并增加细胞内钠，因此可通过钠钙交换增加Cai。镧可阻断钠钙交换，也能阻断氟化物诱导的红细胞钾外流。我们得出结论，氟化物对腺苷酸环化酶的作用在完整组织中并不重要，抑制钠钾ATP酶及随后的钠钙交换可能是急性氟中毒时Cai增加的机制。
