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. 2020 Oct 6;10(10):233.
doi: 10.3390/life10100233.

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

Aude Lafoux  1 , Sabine Lotteau  2 , Corinne Huchet  3 , Sylvie Ducreux  2   4
Affiliations

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

Aude Lafoux et al. Life (Basel). .

Abstract

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.

Keywords: TRPV1; exercise; skeletal muscle.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses or interpretation of data; in the writing of the manuscript or in the decision to publish the results.

Figures

Figure 1
Figure 1
Body weight in the different mouse groups. (A,B) Body weight was measured weekly in (A) males and (B) females. Data are means ± standard error of the mean (SEM; n = 4–6). a p < 0.05, b p < 0.01, c p < 0.001, d p < 0.0001 (two-way ANOVA) compared to the control WT sedentary group; (C) scatter plots of body weight at the end of the treadmill protocol. Sedentary animals (left) and (right) active animals. Black symbols—wild-type (WT) mice; red symbols—TRPV1−/− mice; circles—males; triangles—females; plain symbols—sedentary animals; open symbols—active animals. Sample sizes appear within bars (bottom). Three-way ANOVA results presented in Table S1.
Figure 2
Figure 2
Absolute and relative muscle weights into the different mouse groups. Scatter plots of the (A,C,E,G,I) absolute and (B,D,F,H,J) relative weights of (A,B) heart, (C,D) diaphragm, (TA; E,F) tibialis anterior, (EDL; G,H) extensor digitorum longus and (SOL; I,J) soleus muscles. Sedentary animals (left) and (right) active animals. Black symbols—WT mice; red symbols—TRPV1−/− mice; circles—males; triangles—females. Relative weights normalized to body weight (mg/g). Bars represent means. Sample sizes appear within bars (bottom). Three-way ANOVA results presented in Tables S1–S4.
Figure 3
Figure 3
Grip strength tests into the different mouse groups. Scatter plots of the relative maximal muscle strength of (A) forelimbs (2 paws) and (B) combined forelimbs and hind limbs (4 paws). Sedentary animals (left) and (right) active animals. Black symbols—WT mice; red symbols—TRPV1−/− mice; circles—males; triangles—females. Results normalized to body weight (g/g). Bars represent means. Sample sizes appear within bars (bottom). Three-way ANOVA results presented in Table S5.
Figure 4
Figure 4
Contractile properties of isolated slow- and fast-twitch skeletal muscles in male mice under sedentary conditions. Representative twitch traces of extensor digitorum longus (EDL) and soleus (SOL) muscles from sedentary male wild-type (WT, black lines) and TRPV1−/− (TRPV−/−, red lines) mice. Twitches elicited by a single stimulation 0.5 ms duration and six-volt amplitude at room temperature.
Figure 5
Figure 5
In vitro comparison of twitch and tetanus parameters of extensor digitorum longus (EDL) and soleus (SOL) muscles into the different mouse groups. Scatter plots of the (A,B) relative peak tension, (C,D) time-to-peak tension, (E,F) half-relaxation time, (Tmax; G,H) relative tetanic force and (Tmax/t; I,J) twitch/tetanus ratio in (A,C,E,G,I) EDL fast-twitch muscle, and (B,D,F,H,J) SOL slow-twitch muscle. Sedentary animals (left) and (right) active animals. Black symbols—WT mice; red symbols—TRPV1−/− mice; circles—males; triangles—females. Results normalized to the muscle weight (g/mg). Bars represent means. Sample sizes appear within bars (bottom). Three-way ANOVA results presented in Tables S6–S8.
Figure 6
Figure 6
Force–voltage and force–frequency relationships of extensor digitorum longus (EDL) and soleus (SOL) muscles into the different mouse groups. (A,C,E,G) In vitro EDL and (B,D,F,H) SOL relative muscle (A–D) force–voltage and (E–H) force–frequency relationships in (A,B,E,F) male and (C,D,G,H) female mice. Black symbols—WT mice; red symbols—TRPV1−/− mice; circles—males, triangles—females; plain symbols—sedentary animals; open symbols—active animals. Results presented as means ± SEM (n = 4–5) and normalized to muscle weight (g/mg). Three-way ANOVA results presented in Tables S9 and S10.
Figure 7
Figure 7
Fatigue of EDL and SOL muscles into the different mouse groups. In vitro EDL (A,C) and SOL (B,D) relative tetanus amplitude in the fatigue protocol obtained in male (A,B) and female (C,D) mice at fatigue, and 5 and 10 min recovery times. Black symbols—WT mice; red symbols—TRPV1−/− mice; circles—males; triangles—females; plain symbols—sedentary animals; open symbols—active animals. Results presented as means ± SEM (n = 4–5) and normalized to relative pre-fatigue tetanus amplitude (T0). Three-way ANOVA results presented in Tables S11 and S12.
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