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.