Nitric oxide mediates stretch-induced Ca2+ oscillation in smooth muscle

• DOI: 10.1242/jcs.180638
• Publication Date: 2016-06-15T18:11:25Z
• Authors: Ji Zheng; Kui Zhai; Yingxiao Chen; Xu Zhang; Lin Miao; Bin Wei; Guangju Ji
• Keywords: Mice, Knockout; 0303 health sciences; Myocytes, Smooth Muscle; Urinary Bladder; Muscle, Smooth; In Vitro Techniques; Nitric Oxide; Phosphatidylinositol 3-Kinases; 03 medical and health sciences; Guanylate Cyclase; Animals; Inositol 1,4,5-Trisphosphate Receptors; Calcium Signaling; Stress, Mechanical; Enzyme Inhibitors

ABSTRACT The stretching of smooth muscle tissue modulates contraction through augmentation of Ca2+ transients, but the mechanism underlying stretch-induced Ca2+ transients is still unknown. We found that mechanical stretching and maintenance of mouse urinary bladder smooth muscle strips and single myocytes at 30% and 18% beyond the initial length, respectively, resulted in Ca2+ oscillations. Experiments indicated that mechanical stretching remarkably increased the production of nitric oxide (NO) as well as the amplitude and duration of muscle contraction. Stretch-induced Ca2+ oscillations and contractility increases were completely abolished by the NO inhibitor L-NAME or eNOS (also known as NOS3) gene inactivation. Moreover, exposure of eNOS-knockout myocytes to exogenous NO donor induced Ca2+ oscillations. The stretch-induced Ca2+ oscillations were greatly inhibited by the selective inositol 1,4,5-trisphosphate receptor (IP3R) inhibitor xestospongin C and partially inhibited by ryanodine. Moreover, the stretch-induced Ca2+ oscillations were also suppressed by the phosphoinositide 3-kinase (PI3K) inhibitor LY294002, but not by the soluble guanylyl cyclase (sGC) inhibitor ODQ. These results suggest that stretching myocyte and maintenance at a certain length results in Ca2+ oscillations that are NO dependent , and sGC and cGMP independent, and results from the activation of PI3K in smooth muscle.