López M G, Villarroya M, Lara B, Martínez Sierra R, Albillos A, García A G, Gandía L
Departamento de Farmacología, Facultad de Medicina, Universidad Autónoma de Madrid, Spain.
FEBS Lett. 1994 Aug 8;349(3):331-7. doi: 10.1016/0014-5793(94)00696-2.
Potassium-stimulated catecholamine release from superfused bovine adrenal chromaffin cells (70 mM K+ in the presence of 2 mM Ca2+ for 10 s, applied at 5-min intervals) was inhibited by the dihydropyridine furnidipine (3 microM) by 50%. omega-Conotoxin MVIIC (CTx-MVIIC, 3 microM) also reduced the secretory response by about half. Combined CTx-MVIIC plus furnidipine blocked 100% catecholamine release. 45Ca2+ uptake and cytosolic Ca2+ concentrations ([Ca2+]i) in K(+)-depolarized cells were partially blocked by furnidipine or CTx-MVIIC, and completely inhibited by both agents. The whole cell current through Ca2+ channels carried by Ba2+ (IBa) was partially blocked by CTx-MVIIC. Although omega-conotoxin GVIA (CTx-GVIA, 1 microM) and omega-agatoxin IVA (Aga-IVA, 0.2 microM) partially inhibited 45Ca2+ entry, IBa and the increase in [Ca2+]i, the combination of both toxins did not affect the K(+)-evoked secretory response. The results are compatible with the presence in bovine chromaffin cells of a Q-like Ca2+ channel which has a prominent role in controlling exocytosis. They also suggest that Q- and L-type Ca2+ channels, but not N- or P-types are localized near exocytotic active sites in the plasmalemma.
钾离子刺激下，从经超灌流的牛肾上腺嗜铬细胞中释放儿茶酚胺（在存在2 mM钙离子的情况下，以5分钟的间隔施加70 mM钾离子，持续10秒），被二氢吡啶类药物福尼地平（3 microM）抑制了50%。ω-芋螺毒素MVIIC（CTx-MVIIC，3 microM）也使分泌反应降低了约一半。联合使用CTx-MVIIC和福尼地平可阻断100%的儿茶酚胺释放。在钾离子去极化的细胞中，45钙离子摄取和胞质钙离子浓度（[Ca2+]i）被福尼地平或CTx-MVIIC部分阻断，而被两种药物共同作用完全抑制。通过钡离子携带的钙离子通道的全细胞电流（IBa）被CTx-MVIIC部分阻断。尽管ω-芋螺毒素GVIA（CTx-GVIA，1 microM）和ω-阿加毒素IVA（Aga-IVA，0.2 microM）部分抑制了45钙离子内流、IBa以及[Ca2+]i的增加，但两种毒素联合使用并不影响钾离子诱发的分泌反应。这些结果与牛嗜铬细胞中存在一种类似Q型的钙离子通道相符，该通道在控制胞吐作用中起重要作用。它们还表明，Q型和L型钙离子通道，而非N型或P型，定位于质膜中胞吐活性位点附近。
