Modulation of Outward Potassium Currents by Nitric Oxide in Longitudinal Smooth Muscle Cells of Guinea-pig Ileum

Modulation of Outward Potassium Currents by Nitric Oxide in Longitudinal Smooth Muscle Cells of Guinea-pig Ileum

<P> To investigate the possible involvement of outward potassium (K<SUP>+</SUP>) currents in nitric oxide-induced relaxation in intestinal smooth muscle, we used whole-cell patch clamp technique in freshly dispersed guinea-pig ileum longitudinal smooth muscle cells. When cells were held at &#8291;60 mV and depolarized from &#8291;40 mV to &#8290;50 mV in 10 mV increments, sustained outward K<SUP>+</SUP> currents were evoked. The outward K<SUP>+</SUP> currents were markedly increased by the addition of 10 &#12557;M sodium nitroprusside (SNP). 10 &#12557;M S-nitroso-N-acetylpenicillamine (SNAP) and 1 mM 8-Bromo-cyclic GMP (8-Br-cGMP) also showed a similar effect to that of SNP. 1 mM tetraethylammonium (TEA) significantly reduced depolarization-activated outward K<SUP>+</SUP> currents. SNP-enhanced outward K<SUP>+</SUP> currents were blocked by the application of TEA. High EGTA containing pipette solution (10 mM) reduced the control currents and also inhibited the SNP-enhanced outward K<SUP>+</SUP> currents. 5 mM 4-aminopyridine (4-AP) significantly reduced the control currents but showed no effect on SNP-enhanced outward K<SUP>+</SUP> currents. 0.3 &#12557;M apamin and 10 &#12557;M glibenclamide showed no effect on SNP-enhanced outward K<SUP>+</SUP> currents. 10 &#12557;M 1H-[1,2,4]oxadiazolo [4,3-a]quinoxaline-1-one (ODQ), a specific inhibitor of soluble guanylate cyclase, significantly blocked SNP-enhanced K<SUP>+</SUP> currents. We conclude that NO donors activate the Ca<SUP>2+</SUP>-activated K<SUP>+</SUP> channels in guinea-pig ileal smooth muscle via activation of guanylate cyclase.