Role of sarcoplasmic reticulum in inhibitory junction potentials and hyperpolarizations by nitric oxide donors in opossum oesophagus

1 Previous patch clamp studies of oesophageal circular muscle cells showed that nitric oxide (NO) modulated the opening of Ca2+-activated K+ channels involved in mediating the inhibitory junction potentials (i.j.ps). This study clarified the role of Ca2+ release from the superficial sarcoplasmic reticulum (SR) in the mechanism of i.j.ps or hyperpolarizing responses to NO-releasing compounds. Electrical and mechanical activities were simultaneously recorded by intracellular microelectrode or double sucrose gap techniques. 2 The NO-donors, sydnonimine (SIN-I) and sodium nitroprusside, each at 500 mu M, hyperpolarized oesophageal circular muscle cells by 15-20 mV, like i.j.ps. 3 The selective inhibitors of SR Ca2+-ATPase (cyclopiazonic acid 10-30 mu M and thapsigargin 5 mu M) and the SR Ca2+ release channel activator (ryanodine 30 mu M) caused depolarization and spontaneous contractions which were diminished after prolonged (>30 min) incubation with these agents in Ca2+-containing medium. Moreover, these agents inhibited both the i.j.p. and NO-donor hyperpolarizations, suggesting that a functional SR Ca2+ uptake is necessary for the response to endogenous or exogenous NO. 4 These results, along with our previous findings of the dependence of i.j.ps and NO-donor hyperpolarizations on K+ channel activation and cyclic GMP elevation, support the hypothesis that subplasmalemmal Ca-i(2+) elevation, via vectorial Ca2+ release from superficial SR toward the plasmalemma, may be an important mechanism by which NO, from NO-liberating compounds or released from inhibitory neurones induces relaxation and i.j.ps in opossum oesophagus.