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

2020 ◽  
Vol 5 (6) ◽  
pp. 370-377
Author(s):  
V. O. Stetska ◽  
◽  
O. F. Moroz ◽  
T. V. Dovbynchuk ◽  
G. M. Tolstanova ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Transit Time ◽  
Transient Receptor Potential ◽  
Contractile Activity ◽  
Receptor Potential ◽  
Muscle Cells ◽  
Transient Receptor Potential Vanilloid ◽  
Transient Receptor

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

Molecular determinants of PKA-dependent inhibition of TRPC5 channel

2011 ◽  
Vol 301 (4) ◽  
pp. C823-C832 ◽  
Author(s):  
Tae Sik Sung ◽  
Jae Pyo Jeon ◽  
Byung Joo Kim ◽  
Chansik Hong ◽  
Sung Young Kim ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Muscle Cells ◽  
Intestinal Smooth Muscle ◽  
Transient Receptor Potential Vanilloid ◽  
Trpc Channels ◽  
Muscarinic Stimulation ◽  
Transient Receptor

Canonical transient receptor potential (TRPC) channels are Ca2+-permeable, nonselective cation channels that are widely expressed in numerous cell types. Here, we demonstrate a new mechanism of TPRC isofom 5 (TRPC5) regulation, via cAMP signaling via Gαs. Monovalent cation currents in human embryonic kidney-293 cells transfected with TRPC5 were induced by G protein activation with intracellular perfusion of GTPγS or by muscarinic stimulation. This current could be inhibited by a membrane-permeable analog of cAMP, 8-bromo-cAMP, by isoproterenol, by a constitutively active form of Gαs [Gαs (Q227L)], and by forskolin. These inhibitory effects were blocked by the protein kinase A (PKA) inhibitors, KT-5720 and H-89, as well as by two point mutations at consensus PKA phosphorylation sites on TRPC5 (S794A and S796A). Surface expression of several mutated versions of TRPC5, quantified using surface biotinylation, were not affected by Gαs (Q227L), suggesting that trafficking of this channel does not underlie the regulation we report. This mechanism of inhibition was also found to be important for the closely related channel, TRPC4, in particular for TRPC4α, although TRPC4β was also affected. However, this form of regulation was not found to be involved in TRPC6 and transient receptor potential vanilloid 6 function. In murine intestinal smooth muscle cells, muscarinic stimulation-induced cation currents were mediated by TRPC4 (>80%) and TRPC6. In murine intestinal smooth muscle cells, 8-bromo-cAMP, adrenaline, and isoproterenol decreased nonselective cation currents activated by muscarinic stimulation or GTPγS. Together, these results suggest that TRPC5 is directly phosphorylated by Gs/cAMP/PKA at positions S794 and S796. This mechanism may be physiologically important in visceral tissues, where muscarinic receptor and β2-adrenergic receptor are involved in the relaxation and contraction of smooth muscles.

scholarly journals Attenuation of Canonical Transient Receptor Potential-Like Channel 6 Expression Specifically Reduces the Diacylglycerol-Mediated Increase in Intracellular Calcium in Human Myometrial Cells

Endocrinology ◽  
2010 ◽  
Vol 151 (1) ◽  
pp. 406-416 ◽  
Author(s):  
Daesuk Chung ◽  
Yoon-Sun Kim ◽  
Jennifer N. Phillips ◽  
Aida Ulloa ◽  
Chun-Ying Ku ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Transient Receptor Potential ◽  
Contractile Activity ◽  
Receptor Potential ◽  
Myometrial Cells ◽  
Canonical Transient Receptor Potential ◽  
Voltage Dependent ◽  
Transient Receptor ◽  
Entry Mechanism

Abstract An increase in intracellular Ca2+ ([Ca2+]i) as a result of release of Ca2+ from intracellular stores or influx of extracellular Ca2+ contributes to the regulation of smooth muscle contractile activity. Human uterine smooth muscle cells exhibit receptor-, store-, and diacylglycerol (OAG)-mediated extracellular Ca2+-dependent increases in [Ca2+]i (SRCE) and express canonical transient receptor potential-like channels (TRPC) mRNAs (predominantly TRPC1, -4, and -6) that have been implicated in SRCE. To determine the role of TRPC6 in human myometrial SRCE, short hairpin RNA constructs were designed that effectively targeted a TRPC6 mRNA reporter for degradation. One sequence was used to produce an adenovirus construct (TC6sh1). TC6sh1 reduced TRPC6 mRNA but not TRPC1, -3, -4, -5, or -7 mRNAs in PHM1-41 myometrial cells. Compared with uninfected cells or cells infected with empty vector, the increase in [Ca2+]i in response to OAG was specifically inhibited by TC6sh1, whereas SRCE responses elicited by either oxytocin or thapsigargin were not changed. Similar findings were observed in primary pregnant human myometrial cells. When PHM1-41 cells were activated by OAG in the absence of extracellular Na+, the increase in [Ca2+]i was partially reduced. Furthermore, pretreatment with nifedipine, an L-type calcium channel blocker, also partially reduced the OAG-induced [Ca2+]i increase. Similar effects were observed in primary human myometrial cells. These findings suggest that OAG activates channels containing TRPC6 in myometrial cells and that these channels act via both enhanced Na+ entry coupled to activation of voltage-dependent Ca2+ entry channels and a nifedipine-independent Ca2+ entry mechanism to promote elevation of intracellular Ca2+.

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