Insulin inhibits voltage-dependent calcium influx into rod photoreceptors.
Insulin inhibits the ERG b-wave and modulates L-type calcium currents (I(Ca)) in various preparations. We therefore examined insulin's effects on I(Ca) and depolarization-evoked [Ca2+]i increases in rod photoreceptors. Insulin inhibited I(Ca) and caused a dose-dependent reduction in the depolarization-evoked Ca2+ influx with an EC50 of 2.1 nM. Tyrosine kinase inhibitors, lavendustin A (100 nM) and genistein (10 microM), prevented insulin from reducing the depolarization-evoked Ca2+ increase in rods. Their less active analogues, lavendustin B and daidzein, had similar effects. An insulin receptor-specific tyrosine kinase inhibitor, HNMPA-(AM)3 (50 microM), prevented insulin (30 nM) from reducing the depolarization-evoked Ca2+ increase in rods. The results suggest that insulin inhibits Ca2+ influx through voltage-dependent I(Ca) in rod photoreceptors via tyrosine kinase activity.
Stella
S L
SL
Department of Pharmacology, University of Nebraska Medical Center, Omaha 68198-5540, USA.
Bryson
E J
EJ
Thoreson
W B
WB
D000557:Ambystoma; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology*; D015640:Ion Channel Gating / Q000187:drug effects*; D008564:Membrane Potentials / Q000187:drug effects; D018408:Patch-Clamp Techniques; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D017948:Retinal Rod Photoreceptor Cells / Q000187:drug effects / Q000378:metabolism*
D015220:Calcium Channels; D004791:Enzyme Inhibitors; D007004:Hypoglycemic Agents; D007328:Insulin; D011505:Protein-Tyrosine Kinases; D002118:Calcium