omega-Conotoxin-sensitive, voltage-operated Ca2+ channels in insulin-secreting cells.
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.
Sher
E
E
Department of Medical Pharmacology, University of Milan, Italy.
Biancardi
E
E
Pollo
A
A
Carbone
E
E
Li
G
G
Wollheim
C B
CB
Clementi
F
F
D000818:Animals; D001667:Binding, Competitive; D002121:Calcium Channel Blockers / Q000378:metabolism / Q000494:pharmacology*; D015220:Calcium Channels / Q000378:metabolism / Q000502:physiology*; D002460:Cell Line; D004558:Electric Stimulation; D004594:Electrophysiology; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D010456:Peptides, Cyclic / Q000378:metabolism / Q000494:pharmacology*; D011233:Precipitin Tests; D051381:Rats; D020960:omega-Conotoxins
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D007328:Insulin; D010456:Peptides, Cyclic; D020960:omega-Conotoxins; C053423:Conus magus toxin