Nitric oxide donors enhanced Ca2+ currents and blocked noradrenaline-induced Ca2+ current inhibition in rat sympathetic neurons.
1. The effects of NO donors on Ca2+ channel currents and noradrenaline (NA)-induced Ca2+ current inhibition were investigated in superior cervical ganglion (SCG) neurons using the whole-cell patch-clamp technique. 2. A 500 microM concentration of the NO donors, sodium nitroprusside (SNP) and S-nitroso-N-acetylpenicillamine (SNAP), enhanced Ca2+ current amplitude after either extracellular or intracellular application. The magnitude of Ca2+ current enhancement induced by NO donors was greater after intracellular application than after extracellular application. 3. Intracellular application of 1 mM guanosine 3',5'-cyclic monophosphate (cGMP) or 100 microM M&B 22948 (2-O-propoxyphenyl-8-azapurine-6-one), a cGMP phosphodiesterase inhibitor, or extracellular application of 1 mM 8-bromoguanosine 3',5'-cyclic monophosphate (8-Br-cGMP) also increased the amplitude of Ca2+ currents thus mimicking the effect of the NO donors on Ca2+ channels. In contrast, pretreatment with Methylene Blue (100 microM) decreased the SNP (500 microM)-induced enhancement of Ca2+ currents. 4. Intracellular application of 500 microM SNP and SNAP, 100 microM M&B 22948 or 1 mM cGMP, or extracellular application of 200 microM 8-Br-cGMP reduced the magnitude of Ca2+ current inhibition induced by 5 microM NA. In addition, 500 microM SNP prevented the NA-induced shift of tail current activation curves to more depolarized potentials. 5. Internal dialysis with 500 microM SNP and SNAP or 1 mM cGMP, or extracellular application of 200 microM 8-Br-cGMP, reduced Ca2+ current facilitation produced by a depolarizing conditioning pulse both in the absence and presence of 5 microM NA. 6. The results suggest that NO donors induce enhancement of Ca2+ currents and block NA-induced Ca2+ current inhibition of SCG neurons via stimulation of cGMP formation.
Chen
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Department of Physiology, Tulane University School of Medicine, New Orleans, LA 70112, USA.
Schofield
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D000818:Animals; D002120:Calcium Channel Agonists / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D003213:Conditioning, Psychological / Q000502:physiology; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009569:Nitric Oxide / Q000737:chemistry / Q000494:pharmacology*; D009638:Norepinephrine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D026423:S-Nitroso-N-Acetylpenicillamine; D017783:Superior Cervical Ganglion / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D013564:Sympathetic Nervous System / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D014665:Vasodilator Agents / Q000494:pharmacology
D002120:Calcium Channel Agonists; D015220:Calcium Channels; D014665:Vasodilator Agents; C016276:8-bromocyclic GMP; D009569:Nitric Oxide; D026423:S-Nitroso-N-Acetylpenicillamine; D010396:Penicillamine; D006152:Cyclic GMP; D009638:Norepinephrine