Sher E, Biancardi E, Pollo A, Carbone E, Li G, Wollheim C B, Clementi F
Department of Medical Pharmacology, University of Milan, Italy.
Eur J Pharmacol. 1992 Jun 17;216(3):407-14. doi: 10.1016/0014-2999(92)90438-a.
The properties of voltage-operated Ca2+ channel subtypes were investigated in insulin-secreting RINm5F cells. Two types of channels were identified: a dihydropyridine-sensitive (L-type) channel, and an omega-conotoxin-sensitive (omega-type) channel. 125I-omega-Conotoxin bound with high affinity (Kd 46.7 pM) to a saturable number of binding sites (10.3 fmol/mg of protein). Toxin binding was not antagonized by L-type channel ligands, but was sensitive to Ca2+ and neomycin. 125I-omega-Conotoxin-labeled Ca2+ channels were recognized by autoantibodies of Lambert-Eaton myasthenic patients. These antibodies are known to be specific for the neuronal omega-type channel. High-voltage-activated Ca2+ currents, investigated with the patch-clamp technique, consisted of a major dihydropyridine-sensitive (L-type) component, and a minor fraction irreversibly blocked by omega-conotoxin. Depolarizing secretagogues, such as D-glyceraldehyde and alanine, induced Ca(2+)-dependent insulin secretion, which was attenuated by omega-conotoxin. Taken together, these results show that voltage-operated Ca2+ channels in insulin-secreting RINm5F cells are heterogeneous and, in particular, that an omega-type channel, pharmacologically, immunologically and electrophysiologically similar to the neuronal omega-type channel, is also expressed in endocrine cells where it might have a role in the control of hormone secretion.
在胰岛素分泌型RINm5F细胞中研究了电压门控Ca2+通道亚型的特性。鉴定出两种类型的通道：一种对二氢吡啶敏感（L型）通道，以及一种对ω-芋螺毒素敏感（ω型）通道。125I-ω-芋螺毒素以高亲和力（Kd 46.7 pM）与可饱和数量的结合位点（10.3 fmol/mg蛋白质）结合。毒素结合不受L型通道配体的拮抗，但对Ca2+和新霉素敏感。125I-ω-芋螺毒素标记的Ca2+通道可被兰伯特-伊顿肌无力患者的自身抗体识别。已知这些抗体对神经元ω型通道具有特异性。用膜片钳技术研究的高电压激活Ca2+电流由主要的二氢吡啶敏感（L型）成分和一小部分被ω-芋螺毒素不可逆阻断的成分组成。去极化促分泌剂，如D-甘油醛和丙氨酸，诱导Ca(2+)依赖性胰岛素分泌，而ω-芋螺毒素可减弱这种分泌。综上所述，这些结果表明胰岛素分泌型RINm5F细胞中的电压门控Ca2+通道是异质性的，特别是一种在药理学、免疫学和电生理学上与神经元ω型通道相似的ω型通道，也在内分泌细胞中表达，它可能在激素分泌的控制中发挥作用。
