This application proposes to study the properties of CNG channels in cone synaptic terminals of the lizard. These terminals are large and therefore suitable for localized electrophysiological experiments and calcium imaging. The premise is that these CNG channels are involved in calcium influx and regulation of cone transmitter release. The first specific aim is to characterize the pharmacology of the CNG channel, and in particular to find specific antagonists. Two prospects are a Conus toxin and cyclic nucleotide analogs. The second specific aim is to investigate the role of CNG channels in calcium influx and to compare this influx with that generated by voltage dependent calcium channels in the terminal. The third specific aim is to determine the role of CNG channels in triggering transmitter release from cones. Catfish horizontal cells will be used as a """"""""biosensor"""""""" to detect the cone's glutamate release. The final specific aim is to determine the role of CNG channels in mediating the release of cone transmitter in the presence of nitric oxide (NO). Since NO affects both CNG and voltage-gated calcium channels, the relative significance of these two pathways will be determined. Preliminary results indicate that NO produces a sag in light response of horizontal cells in the intact retina. Whether this is due to effects on cones or effects on horizontal cells will be examined.
| Savchenko, A; Kraft, T W; Molokanova, E et al. (2001) Growth factors regulate phototransduction in retinal rods by modulating cyclic nucleotide-gated channels through dephosphorylation of a specific tyrosine residue. Proc Natl Acad Sci U S A 98:5880-5 |
| Molokanova, E; Kramer, R H (2001) Mechanism of inhibition of cyclic nucleotide-gated channel by protein tyrosine kinase probed with genistein. J Gen Physiol 117:219-34 |
| Kramer, R H; Molokanova, E (2001) Modulation of cyclic-nucleotide-gated channels and regulation of vertebrate phototransduction. J Exp Biol 204:2921-31 |
| Molokanova, E; Maddox, F; Luetje, C W et al. (1999) Activity-dependent modulation of rod photoreceptor cyclic nucleotide-gated channels mediated by phosphorylation of a specific tyrosine residue. J Neurosci 19:4786-95 |
| Molokanova, E; Savchenko, A; Kramer, R H (1999) Noncatalytic inhibition of cyclic nucleotide-gated channels by tyrosine kinase induced by genistein. J Gen Physiol 113:45-56 |
