OMEGA-CONOTOXIN-SENSITIVE, VOLTAGE-OPERATED CA-2+ CHANNELS IN INSULIN-SECRETING CELLS

被引:46
作者
SHER, E
BIANCARDI, E
POLLO, A
CARBONE, E
LI, GD
WOLLHEIM, CB
CLEMENTI, F
机构
[1] UNIV TURIN,DEPT ANAT & HUMAN PHYSIOL,I-10124 TURIN,ITALY
[2] CTR MED UNIV GENEVA,DIV BIOCHIM CLIN,CH-1211 GENEVA 4,SWITZERLAND
关键词
INSULIN SECRETION; CA-2+ CHANNELS; OMEGA-CONOTOXIN;
D O I
10.1016/0014-2999(92)90438-A
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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. I-125-omega-Conotoxin bound with high affinity (K(d) 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. I-125-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 Ca2+-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.
引用
收藏
页码:407 / 414
页数:8
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