Myogenic NOS in canine lower esophageal sphincter: enzyme activation, substrate recycling, and product actions

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Abstract
Depolarization elicited outward K+currents from canine lower esophageal sphincter (LES) muscle cells, primarily through iberiotoxin (IbTX)- and tetraethylammonium-sensitive Ca2+-dependent K+channels. Current magnitudes varied with pipette Ca2+concentration (EC50= 108.5 nM). NG-nitro-l-arginine (l-NNA, 10−4M), IbTX (10−8M), or buffering intracellular Ca2+to 8 nM decreased outward currents >80%. Sodium nitroprusside (NaNP, 10−4M) restoredl-NNA-inhibited or low intracellular Ca2+concentration (not IbTX)-inhibited currents.l-NNA or IbTX application depolarized LES cells from −43 to −35 mV. NaNP restored the membrane potential to −46 mV afterl-NNA but not after IbTX application. Nifedipine (30 μM) reduced outward currents and abolished or reduced l-NNA or NaNP effects, respectively. Immunocytochemistry revealed the presence of both argininosuccinate synthetase and argininosuccinate lyase in LES muscle cells. l-Citrulline, likel-arginine, reversedl-NNA inhibition of outward currents; only l-arginine reversed inhibition of outward currents by an antibody to argininosuccinate synthetase. Therefore, endogenous nitric oxide production, activated by Ca2+entrance involving l-type Ca2+channels, may continuously enhance outward currents to modulate LES muscle cell membrane potential and excitability.