Inhibition of carbachol-evoked oscillatory currents by the NO donor sodium nitroprusside in guinea-pig ileal myocytes

The effect of sodium nitroprusside (SNP) on carbachol (CCh)-evoked inward cationic current ( I cat ) oscillations in guinea-pig ileal longitudinal myocytes was investigated using the whole-cell patch-clamp technique and permeabilized longitudinal muscle strips. SNP (10 μ m ) completely inhibited I cat oscillations evoked by 1 μ m CCh. 1H-(1,2,4) Oxadiazole [4,3-a] quinoxaline-1-one (ODQ; 1 μ m ) almost completely prevented the inhibitory effect of SNP on I cat oscillations. 8-Bromo-guanosine 3′,5′-cyclic monophosphate (8-Br-cGMP; 30 μ m ) in the pipette solution completely abolished I cat oscillations. However, a pipette solution containing Rp-8-Br-cGMP (30 μ m ) almost completely abolished the inhibitory effect of SNP on I cat oscillations. When the intracellular calcium concentration ([Ca 2+ ] i ) was held at a resting level using BAPTA (10 m m ) and Ca 2+ (4.6 μ m ) in the pipette solution, CCh (1 μ m ) evoked only the sustained component of I cat without any oscillations and SNP did not affect the current. A high concentration of inositol 1,4,5-trisphosphate (IP 3 ; 30 μ m ) in the patch pipette solutions significantly reduced the inhibitory effect of SNP (10 μ m ) on I cat oscillations. SNP significantly inhibited the Ca 2+ release evoked by either CCh or IP 3 but not by caffeine in permeabilized preparations of longitudinal muscle strips. These results suggest that the inhibitory effects of SNP on I cat oscillations are mediated, in part, by functional modulation of the IP 3 receptor, and not by the inhibition of cationic channels themselves or by muscarinic receptors in the plasma membrane. This inhibition seems to be mediated by an increased cGMP concentration in a protein kinase G-dependent manner.