DISSOCIATION BETWEEN ELECTRICAL AND MECHANICAL RESPONSES TO NITRERGICSTIMULATION IN THE CANINE GASTRIC FUNDUS

1.We examined the relationships between membrane potential, intracellu lar [Ca2+] ([Ca2+](i)), and tension in muscles of the canine gastric f undus in response to nitrergic stimulation by NO donors and electrical field stimulation (EFS) of intrinsic enteric inhibitory neurons when adrenergic and cholinergic responses were blocked. 2. NO donors reduce d [Ca2+](i) and tension in a concentration-dependent manner. A close r elationship was noted between these parameters. 3. In terms of the [Ca 2(+)] vs. force relationship, relaxation responses to EFS differed fro m responses to NO donors. EFS resulted in smaller decreases in [Ca2+]( i) to produce a given relaxation compared with responses to NO donors. Thus, muscles stimulated with EFS were less sensitive to [Ca2+](i) th an muscles stimulated with exogenous NO. 4. When membrane potential, [ Ca2+](i) and tension were monitored simultaneously in the same muscles , a temporal dissociation was noted between the electrical responses a nd changes in [Ca2+](i) and tension. Brief electrical responses were a ssociated with more sustained changes in [Ca2+](i) and tension. 5. Fur ther dissociation between electrical and mechanical effects was noted. Changes in [Ca2+](i) and tension caused by sodium nitroprusside and E FS were blocked by arginine analogues and by oxyhaemoglobin, but elect rical responses were unaffected. 1-H-[1,2,4] oxadiazolo-[4,3-a]quinoxa lin-1-one (ODQ), an inhibitor of soluble guanylyl cyclase, also blocke d the effects of nitrergic stimulation on [Ca2+](i) and tension, witho ut affecting hyperpolarization. Thus, in the presence of continued hyp er-polarization, the reductions in [Ca2+](i) and tension caused by nit rergic stimulation were blocked. 6. Block of hyperpolarization in resp onse to nitrergic stimulation with tetrapentylammonium chloride (TPEA) had relatively little effect on the [Ca2+](i) and tension responses. Thus, hyperpolarization is not required for nitrergic effects on [Ca2](i) and tension. 7. In summary reduction in [Ca2+](i) and tension in response to nitrergic stimulation of the canine gastric fundus does no t depend upon electrical hyperpolarization. Non-electrical mechanisms such as enhanced uptake of Ca2+ by the sarcoplasmic reticulum or reduc tion in the Ca2+ sensitivity of the contractile apparatus may be the p rimary mechanisms mediating nitrergic responses in these muscles.