Effects of nitric oxide in cultured prevertebral sympathetic ganglion neurons

The effects of the nitric oxide donor, S-nitrosoacetylpenicillamine (SNAP), were tested on cultured dissociated guinea pig celiac ganglion neurons using whole cell patch-clamp recordings. S-nitrosoacetylpenicillamine induced a concentration- and voltage-dependent inwardly directed shift in holding current (inward current shift) in 89% of neurons. The inward current shift was prevented by pre-treatment with the nitric oxide scavenger reduced hemoglobin and was abolished by intra- or extracellular cesium. The amplitude of the inward current shift was also sensitive to the extracellular potassium concentration. The S-nitrosoacetylpenicillamine-induced inward current shift was mediated by a decrease in calcium-dependent potassium currents (1(AHPs)); apamin (100 nM), charybdotoxin (10 nM) or tetraethylammonium (5 mM) reduced but did not abolish the amplitude of its inward current shift and a combination of apamin and tetraethylammonium abolished the S-nitrosoacetylpenicillamine-induced inward current response. In the presence of extracellular cobalt, SNAP produced an outward current that was concentration- and voltage-dependent, abolished by reduced hemoglobin and extracellular cesium and reduced by 4-AP (1 mM); in the absence of cobalt, 4-AP increased the SNAP-induced inward current shift. These data indicate that NO exerts dual opposing effects on neuronal potassium conductances, namely an inward current shift mediated through an inhibition of I-AHP and induction of an outward current mediated by activation of the potassium delayed rectifier.