Regional differences of energetics, mechanics, and kinetics of myosin cross-bridge in human ureter smooth muscle

This study provides information about baseline mechanical properties of the entire muscle and the molecular contractile mechanism in human ureter smooth muscle and proposed to investigate if changes in mechanical motor performance in different regions of isolated human ureter are attributable to differences in myosin crossbridge interactions. Classic mechanical, contraction and energetic parameters derived from the tension-velocity relationship were studied in ureteral smooth muscle strips oriented longitudinally and circularly from abdominal and pelvic human ureter parts. By applying of Huxley’s mathematical model we calculated the total working crossbridge number per mm2 (Ψ), elementary force per single crossbridge (Π0), duration of maximum rate constant of crossbridge attachment 1/f1 and detachment 1/g2 and peak mechanical efficiency (Eff.max). Abdominal longitudinal smooth muscle strips exhibited significantly higher maximum isometric tension and faster maximum unloaded shortening velocity compared to pelvic ones. Contractile differences were associated with significantly higher crossbridge number per mm2. Abdominal longitudinal muscle strips showed a lower duration of maximum rate constant of crossbridge attachment and detachment and higher peak mechanical efficiency than pelvic ones. Such data suggest that the abdominal human ureter showed better mechanical motor performance mainly related to a higher crossbridge number and crossbridge kinetics differences. Such results were more evident in the longitudinal rather than in the circular layer

Origin of motion in the human ureter: mechanics, energetics and kinetics of the myosin molecular motors

Background: Ureteral peristalsis is the result of coordinated mechanical motor performance of longitudinal and circular smooth muscle layer of the ureter wall. The main aim of this study was to characterize in smooth muscle of proximal segments of human ureter, the mechanical properties at level of muscle tissue and at level of myosin molecular motors. Methods: Ureteral samples were collected from 15 patients, who underwent nephrectomy for renal cancer. Smooth muscle strips longitudinally and circularly oriented from proximal segments of human ureter were used for the in vitro experiments. Mechanical indices including the maximum unloaded shortening velocity (Vmax), and the maximum isometric tension (P0) normalized per cross-sectional area, were determined in vitro determined in electrically evoked contractions of longitudinal and circular smooth muscle strips. Myosin cross-bridge (CB) number per mm2 (Ψ) the elementary force per single CB (Ψ) and kinetic parameters were calculated in muscle strips, using Huxley’s equations adapted to nonsarcomeric muscles. Results: Longitudinal smooth muscle strips exhibited a significantly (p<0.05) faster Vmax (63%) and a higher P0 (40%), if compared to circular strips. Moreover, longitudinal muscle strips showed a significantly higher unitary force (Ψ) per CB. However, no significant differences were observed in CB number, the attachment (f1) and the detachment (g2) rate constants between longitudinal and circular muscle strips. Conclusions: The main result obtained in the present work documents that the mechanical, energetic and unitary forces per CB of longitudinal layer of proximal ureter are better compared to the circular one; these preliminary findings suggested, unlike intestinal smooth muscle, a major role of longitudinal smooth muscle layer in the ureter peristalsis

Conformational studies of tedarenes, two cyclic diarylheptanoids from the sponge Tedania ignis

Diarylheptanoids (DHs) are an unusual class of natural products composed of two aromatic rings linked by a C7 chain. They showed interesting biological activities, including leishmanicidal and antiprotozoal,1 antitumor, antioxidant, anti-ischemic, anti-inflammatory, and inhibitory against NO production. In addition to the more common linear DHs, there is a smaller number of cyclic DHs, formed from the linear type by phenolic oxidative coupling.3 The isolation and structural elucidation of two new cyclic diarylheptanoids (the diaryl ether 1 and the diphenyl 2) from the marine sponge Tedania ignis will be presented. Compound 1, but not compound 2, inhibits NO production. The conformational equilibria of the two molecules, which made their apparently simple structure elucidation a challenging process, will be discussed