Na+/Ca2+ exchanger 1/2 double-heterozygote knockout mice display increased nitric oxide component and altered colonic motility

The na+/ca2+ exchanger (ncx) is a plasma membrane transporter involved in regulating intracellular ca2+ concentrations. ncx is critical for ca2+ regulation in cardiac muscle,vascular smooth muscle,and nerve fibers. to determine the role of ncx1 and ncx2 in gastrointestinal tissues,we examined electric field stimulation (efs)-induced responses in the longitudinal smooth muscle of the distal colon in ncx1 and ncx2 double-heterozygote knockout mice (double het). we found that the amplitudes of efs-induced relaxation that persisted during efs were greater in double het than in wild-type mice (wt). under the non-adrenergic,non-cholinergic (nanc) condition,efs-induced relaxation in double het was similar in amplitude to that of wt. in the experiments in which l-nna was added under nanc conditions following the efs,the magnitudes of efs-induced relaxation were smaller in double het than those in wt. in addition,an ncx inhibitor,sn-6,enhanced efs-induced relaxation but did not affect efs-induced relaxation under nanc condition,as in double het. moreover,the magnitudes of relaxation induced by nor-1,which generates no,were greater in double het compared with wt. similarly,sn-6 potentiated the magnitudes of nor-1-induced relaxation. in this study,we demonstrate that ncx regulate colonic motility by altering the sensitivity of the inhibitory component. © the japanese pharmacological society.