Modulation of hybrid bass retinal gap junctional channel gating by nitric oxide.
1. To elucidate the role of the nitric oxide (NO) transmitter system in the regulation of gap junctional channel gating, we have examined the effects of the NO donor sodium nitroprusside (SNP) on the electrical synapses of hybrid bass H2-type horizontal cells. 2. SNP reversibly reduced the macroscopic junctional conductance without significantly changing voltage sensitivity. 3. Kinetic analyses showed that SNP made the voltage-dependent decay of junctional currents more rapid. 4. Single-channel data showed that SNP reduced channel open probability by reducing channel open frequency. 5. The action of SNP can be prevented or largely reduced by the NO scavenger, haemoglobin. NO release by SNP solutions was detected directly by a NO sensor. 6. NO appears to modulate the gap junctional conductance by activating the cGMP-cGMP-dependent protein kinase G (PKG) pathway. A membrane-permeable cGMP analogue, 8-Br-cGMP, mimics the action of SNP. A soluble guanylate cyclase inhibitor (LY-83583) and a highly specific cGMP-dependent protein kinase inhibitor (RKRARKE) blocked the action of NO. 3-Isobutyl-1-methylxanthine (IBMX), a non-specific phosphodiesterase inhibitor, potentiated the effect of SNP. 7. [Ca2+]i image studies showed that NO donors did not change [Ca2+]i in horizontal cells, suggesting that the regulation of junctional channels by NO is [Ca2+]i independent.
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Department of Physiology, University of Kentucky, Lexington 40536-0084, USA.
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D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000634:Aminoquinolines / Q000494:pharmacology; D000818:Animals; D001492:Bass; D002118:Calcium / Q000378:metabolism; D017630:Connexins / Q000502:physiology*; D017869:Cyclic GMP-Dependent Protein Kinases / Q000378:metabolism; D004594:Electrophysiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology*; D007700:Kinetics; D009569:Nitric Oxide / Q000502:physiology*; D009599:Nitroprusside / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D012160:Retina / Q000187:drug effects / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
D000634:Aminoquinolines; D017630:Connexins; D004791:Enzyme Inhibitors; D010726:Phosphodiesterase Inhibitors; D009599:Nitroprusside; D009569:Nitric Oxide; C041715:6-anilino-5,8-quinolinedione; D017869:Cyclic GMP-Dependent Protein Kinases; D006162:Guanylate Cyclase; D002118:Calcium; D015056:1-Methyl-3-isobutylxanthine