Inhibition of nitric oxide synthase alters light responses and dark voltage of amphibian photoreceptors.
We studied the effects of competitive inhibitors of nitric oxide synthase (L-NMMA and L-NNA) on dark voltage and flash responses of retinal rods of the frog. Substances were applied intracellularly via whole-cell patch-clamp electrodes while the membrane voltage was recorded simultaneously. During recording the exchange of substances by diffusion between cytosol and pipette medium affects the cell's function. Under control conditions this exchange is reflected by a slow hyperpolarization of the dark voltage with time and a prolongated flash response recovery, which is mainly due to a loss of nucleotides. Application of L-NMMA and L-NNA accelerated the spontaneous hyperpolarization of the membrane voltage during the course of an experiment, while the recovery of the flash responses was slowed down. The effects observed upon intracellular application of NO-synthase inhibitors were opposite to those observed previously upon application of sodium nitroprusside. Sodium nitroprusside was much less effective when the intracellular calcium level was decreased by application of EGTA at the same time. It is reasonable to assume that the observed effects are linked to nitric oxide synthase and to a NO-dependent soluble guanylate cyclase. The results suggest that the activity of NO-synthase in photoreceptor cells has an influence on concentration and metabolic flux of cGMP in photoreceptors, which may be of relevance for flash response recovery and adaptation processes. It is likely that the regulation of the soluble guanylate cyclase requires a physiological level of calcium.
Nöll
G N
GN
Physiologisches Institut der Justus-Liebig-Universität, Giessen, Germany.
Billek
M
M
Pietruck
C
C
Schmidt
K F
KF
D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D002118:Calcium / Q000502:physiology; D003624:Darkness; D004594:Electrophysiology; D066298:In Vitro Techniques; D009569:Nitric Oxide / Q000037:antagonists & inhibitors; D019001:Nitric Oxide Synthase; D019335:Nitroarginine; D009599:Nitroprusside / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D010775:Photic Stimulation; D010786:Photoreceptor Cells / Q000187:drug effects* / Q000528:radiation effects*; D011896:Rana temporaria; D017948:Retinal Rod Photoreceptor Cells / Q000187:drug effects / Q000528:radiation effects; D019323:omega-N-Methylarginine
D009599:Nitroprusside; D019335:Nitroarginine; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D002118:Calcium