D–S–Nitrosocysteine Inhibits the Calcium Channels in Rod Photoreceptors

Abstract

Abstract: : Purpose: This study is to elucidate the effects of gaseous NO on calcium channels in rod photoreceptors. L–S–nitrosocysteine (L–SNC), a nitric oxide (NO) generating compound, facilitates Ca²⁺ channels in rods (Kourennyi et al., 1994, Neuron). This facilitation was considered as the effect of gaseous NO, which could be generated physiologically by NO synthase in and near photoreceptors. However, our recent data suggest inhibition of Ca²⁺ channels by gaseous NO, which apparently conflicts with the facilitation by L–SNC. Methods: Isolated rods from the retina of tiger salamander (Ambystoma tigrinum) were used in patch clamp and calcium fluorescence imaging experiments. The animals were handled and sacrificed according to the protocol approved by the University IACUC. L– and D– enantiomers of S–nitrosocysteine (SNC) and sodium nitroprusside (SNP) are used as NO donors. Results: D–SNC inhibited the Ca²⁺ channel conductance (Gmax_drug/Gmax_control = 0.648±0.069, p<0.003). In calcium imaging experiments, the calcium entry induced by high [K⁺]_o was attenuated by D–SNC. Another NO donor of non–thiol type, SNP, also inhibits the Ca²⁺ channel current and calcium entry in rods. Conclusions: Given the fact that D– and L– SNC release equal amount of gaseous NO in the same manner, the differential modulation effects suggest that multiple pathways are involved in the NO modulation of Ca²⁺ channels in rods. Gaseous NO may act as an inhibitor of the Ca²⁺ channels in rods. The previous reported facilitation of Ca²⁺ channels by L–SNC might be due to the transnitrosylation of the channel protein with the S–nitrosothiol type donors.

Keywords: photoreceptors • nitric oxide • ion channels