scholarly journals The Contractile Phenotype of Skeletal Muscle in TRPV1 Knockout Mice Is Gender-Specific and Exercise-Dependent

Life ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. 233
Author(s):  
Aude Lafoux ◽  
Sabine Lotteau ◽  
Corinne Huchet ◽  
Sylvie Ducreux

The transient receptor potential vanilloid 1 (TRPV1) belongs to the transient receptor potential superfamily of sensory receptors. TRPV1 is a non-selective cation channel permeable to Ca2+ that is capable of detecting noxious heat temperature and acidosis. In skeletal muscles, TRPV1 operates as a reticular Ca2+-leak channel and several TRPV1 mutations have been associated with two muscle disorders: malignant hyperthermia (MH) and exertional heat stroke (EHS). Although TRPV1−/− mice have been available since the 2000s, TRPV1’s role in muscle physiology has not been thoroughly studied. Therefore, the focus of this work was to characterize the contractile phenotype of skeletal muscles of TRPV1-deficient mice at rest and after four weeks of exercise. As MS and EHS have a higher incidence in men than in women, we also investigated sex-related phenotype differences. Our results indicated that, without exercise, TRPV1−/− mice improved in vivo muscle strength with an impairment of skeletal muscle in vitro twitch features, i.e., delayed contraction and relaxation. Additionally, exercise appeared detrimental to TRPV1−/− slow-twitch muscles, especially in female animals.

2021 ◽  
Author(s):  
Elena Conte ◽  
Adele Romano ◽  
Michela De Bellis ◽  
Maria Luisa De Ceglia ◽  
Maria Rosaria Carratù ◽  
...  

We explored the involvement of Oxytocin receptor (Oxtr)/ Transient-receptor-potential-vanilloid-1 (TRPV1) genes and Oxytocin (Oxt) on the adaptation of skeletal muscle to cold stress challenge in mice. Oxtr expression in hypothalamic paraventricular (PVN), supraoptic nuclei (SON), and hippocampus (HIPP) were evaluated by immunohistochemistry in parallel with the measurement of circulating Oxt. The Oxtr and TRPV1 gene expression in Soleus (SOL) and Tibialis Anterior (TA) muscles were investigated by RT-PCR. Histological studies of the cardiac muscle after cold stress were also performed. Male mice (n=15) were divided into controls maintained at room temperature (RT=24°C), exposed to cold stress (CS) at T=4°C for 6 hours (6h), and 5 days (5d). Immunohistochemical studies showed that Oxtr protein expression increased by 2-fold (p=0.01) in PVN and by 1.5-fold (p=0.0001) in HIPP after 6h and 5d CS, but decreased by 2-fold (p=0.026) in SON at 5d. Both Oxtr and TRPV1 gene expression increased after 6h and 5d CS in SOL and TA muscles. Oxtr vs TRPV1 gene expression in SOL and TA muscles evaluated by regression analysis was linearly correlated following CS at 6h and 5d but not at control temperature of 24+1°C, supporting the hypothesis of coupling between these genes. The circulating levels of Oxt are unaffected after 6h CS but decreased by 0.2-fold (p=0.0141) after 5d CS. This is the first report that Oxtr and TRPV1 expression are upregulated in response to cold acclimation in skeletal muscle. The up-regulation of Oxtr in PVN and HIPP balances the decrease of circulating Oxt.


2012 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
Xiaoqian Gao ◽  
Sheryl Koch ◽  
Min Jiang ◽  
Nathan Robbins ◽  
Wenfeng Cai ◽  
...  

TRPV2 is a member of transient receptor potential vanilloid (TRPV) family. As a Ca 2+ channel, it can detect various stimuli such as noxious heat (>52°C), membrane stretching, as well as a number of exogenous chemicals, including probenecid, 2-aminoethoxydiphenyl borate, and lysophospholipids. TRPV2 has been found in many tissue types, including neuron and kidney, but the function of TRPV2 in the heart is poorly understood. Here we show TRPV2 is involved in the Ca 2+ cycling process and then regulates the function of the cardiomyocyte. We identified the mRNA expression of TRPV2 in the cardiac tissues of mice using real-time PCR. By performing echocardiography we found that administration of probenecid, a selective TRPV2 agonist, increased cardiac ejection fraction in mice. This positive inotropic effect of probenecid was also shown in Langendorff perfused mice hearts as increased peak +dP/dt. In isolated ventricular myocytes, we found that probenecid significantly increased myocyte fractional shortening in a dose-dependent manner, which was fully blocked by ruthenium red, a non-selective TRPV2 blocker. We also performed fluorescent studies to examine myocyte Ca 2+ cycling. We found that probenecid significantly increased Ca 2+ transient and resting-state Ca 2+ sparks and this effect was eliminated by ruthenium red. When Ca 2+ storage in sarcoplasmic reticulum (SR) was depleted with caffeine, and SR Ca 2+ reuptake was blocked by thapsigargin at the same time, probenecid did not show any effects in either Ca 2+ transient or Ca 2+ sparks. Our patch clamp experiments indicate that probenecid treatment does not trigger any significant transmembrane Ca 2+ influx. These results point to the important role of TRPV2 in regulating SR Ca 2+ release. In conclusion, TRPV2 activation may contribute to increased SR Ca 2+ release, leading to the enhancement of myocyte contractility. Thus, TRPV2 plays a potentially important role in controlling the cellular function of heart.


Author(s):  
Rie Ishizawa ◽  
Han-Kyul Kim ◽  
Norio Hotta ◽  
Gary A. Iwamoto ◽  
Jere H. Mitchell ◽  
...  

The blood pressure response to exercise is exaggerated in type 2 diabetes (T2D). However, the underlying mechanisms remain unclear. It is hypothesized that one mechanism mediating the potentiated cardiovascular response in T2D is the sensitization of chemically sensitive afferent neurons by activation of metaboreceptors. To test this hypothesis, we examined TRPV1 (transient receptor potential vanilloid 1)-induced cardiovascular responses in vivo and muscle afferent discharge ex vivo in T2D rats. Additionally, TRPV1 and PKC (protein kinase C) protein levels in dorsal root ganglia subserving skeletal muscle were assessed. For 14 to 16 weeks, Sprague-Dawley rats were given either a normal diet (control) or a high-fat diet in combination with a low dose (35 and 25 mg/kg) of streptozotocin (T2D). Administration of capsaicin, TRPV1 agonist, in hindlimb evoked significantly greater increases in mean arterial pressure and renal sympathetic nerve activity in decerebrated T2D than control. In a muscle-nerve preparation, the discharge to capsaicin exposure in group IV afferents isolated from T2D was likewise significantly augmented at a magnitude that was proportional to glucose concentration. Moreover, the discharge to capsaicin was potentiated by acute exposure of group IV afferents to a high-glucose environment. T2D showed significantly increased phospholyrated-TRPV1 and -PKCα levels in dorsal root ganglia neurons as compared with control. These findings suggest that group IV muscle afferents are sensitized by PKC-induced TRPV1 overactivity in early stage T2D with hyperglycemia and, thereby, may contribute to the potentiated circulatory response to TRPV1 activation in the disease.


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