The Role of TRPV4 Cation Channels in Smooth Muscle Contractile Activity in Rats

Abstract

Although it was shown that transient receptor potential channels are expressed in the intestinal and myometrial smooth muscle cells and can control gastrointestinal motility and regulate uterine contractility the specific role of transient receptor potential vanilloid-type 4 channel in smooth muscle cells contraction remain largely unknown. The purpose of the study was to test the action of transient receptor potential vanilloid-type 4 selective agonist GSK1016790A on smooth muscle cells contraction in rat’s colon with experimental Parkinson`s disease and in the pregnant rat uterus (18-22 days of gestation). Material and methods. The Parkinson’s disease was induced by single unilateral stereotaxic injection of 12 μg 6-OHDA. The percentage of destroyed dopaminergic neurons was evaluated in apomorphine test (0.5 mg/kg, i.p.) at 1 and 2 weeks after surgery. The water content in faeces was evaluated on the 1st day, then at the 3rd week and 7th month of the experiment. The daily volume of water consumption and gastrointestinal transit time were evaluated at the 3rd week and 7th month after surgery. The action of transient receptor potential vanilloid-type 4 agonist GSK1016790A (0.3 mmol) on smooth muscle cells of colon and myometrium strips contraction was estimated by isometric tension recording. Results and discussion. The apomorphine test showed a progressive increase in the number of turns between the 1st and 2nd week after inducing 6-OHDA-PD. The water content in faeces was increased at the 3rd week (P<0.05) vs. 1st day of the experiment. The rats with 6-OHDA-PD drank less water vs. placebo and intact groups. We observed a 17% delayed GI transit time in 6-OHDA-PD rats (P<0.01) vs. intact and 21% vs. sham-lesioned group of rats 3 weeks after the 6-OHDA treatment. 7 months after the surgery GI transit time was increased more than twice in all studied groups. Transient receptor potential vanilloid-type 4 agonist action on smooth muscle cells of 6-OHDA-PD rats was reduced by 21% compared to intact group and by 46% in sham-lesioned group (P<0.05). After the application of GSK1016790A the rat myometrium strips a 28.4% (P<0.05) decrease of the contractile force was recorded. It was accompanied by a 30.7% (P<0.05) decline of the muscle work estimated as the area under the contractile curve. Suppression of the amplitude of uterine contraction was also followed by a 39.7% (P<0.05) decline of the rise time constant of peaks but unchanged peak duration at the half maximal amplitude. Conclusion. We conclude that pharmacological activation of transient receptor potential vanilloid-type 4 ion channels by their selective agonist GSK1016790A decreased the contractile activity of both colon smooth muscle cells in Parkinson’s disease rats’ model and the myometrium in pregnant rats

Changes in the expression of TRPV4 and TRPM8 channels in the colon of rats with 6-OHDA-induced Parkinson’s disease

“…2, B). In our previous study [15], rats with 6-OHDA-PD at the 7 th month of the experiment had higher levels of water contents in the feces vs. the 3 rd week of the experiment. The water contents in the feces is a marker of colonic inflammation that might be the course of observed less profound GI transit delay on the 7 th month of the experiment.…”

“…In our previous study [14] we used a rat model of easily reproducible partial lesion of the nigrostriatal system (unilateral injection of 6-hydroxydopamine (6-OHDA) and showed reduced spontaneous and carbachol-stimulated colon motor activity in it. Moreover, pharmacological activation of TRPV4 ion channels by their selective agonist GSK1016790A decreased the contractile activity of colon smooth muscle cells in the PD rats model [15].…”

The role of mechanosensitive TRPV4 channels in the regulation of myometrium spontaneous and oxytocin- induced contractility under normal and pathophysiologically relevant conditions

“…Integral force, calculated as the area under the curve (AUC) of contraction transient was by 17% less after agonist administration (p < 0.05) and increased by 77% from this level after the subsequent antagonist application (p < 0.05). Analysis of the correlations between AUC, that represents the work produced by smooth muscle strip, and contraction amplitude of contractile response or its T1/2 demonstrate that the former mainly determinates this parameter (Pearson's r = 0.97) (Stetska et al, 2020). In contrast to the human myometrium, rat smooth muscle strips have demonstrated reduced contraction amplitude and integral force to the 68% and 81% of the control level respectively (p < 0.05).…”