NITRIC-OXIDE DONORS ENHANCED CA2-INDUCED CA2+ CURRENT INHIBITION IN RAT SYMPATHETIC NEURONS( CURRENTS AND BLOCKED NORADRENALINE)

1. The effects of NO donors on Ca2+ channel currents and noradrenaline (NA)-induced Ca2+ current inhibition were investigated in superior ce rvical ganglion (SCG) neurons using the whole-cell patch-clamp techniq ue. 2. A 500 mu M concentration of the NO donors, sodium nitroprusside (SNP) and S-nitroso-N-acetylpenicillamine (SNAP), enhanced Ca2+ curre nt amplitude after either extracellular or intracellular application. The magnitude of Ca2+ current enhancement induced by NO donors was gre ater after intracellular application than after extracellular applicat ion. 3. Intracellular application of 1 mM guanosine 3'5'-cyclic monoph osphate (cGMP) or 100 mu M 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 i ncreased the amplitude of Ca2+ currents thus mimicking the effect of t he NO donors on Ca2+ channels. In contrast, pretreatment with Methylen e Blue (100 mu M) decreased the SNP (500 mu M)-induced enhancement of Ca2+ currents. 4. Intracellular application of 500 mu M SNP and SNAP, 100 mu M M&B 22948 or 1. mM cGMP, or extracellular application of 200 mu M 8-Br-cGMP reduced the magnitude of Ca2+ current inhibition induce d by 5 mu M NA. In addition, 500 mu M SNP prevented the NA-induced shi ft of tail current activation curves to more depolarized potentials. 5 . Internal dialysis with 500 mu M SNP and SNAP or 1 mM cGMP, or extrac ellular application of 200 mu M and Br-cGMP, reduced Ca2+ current faci litation produced by a depolarizing conditioning pulse both in the abs ence and presence of 5 mu M 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.