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

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.

Contractile force assessment methods for in vitro skeletal muscle tissues

“…Interestingly, for the force transducer platform, we found that the tetanic-to-twitch ratio was significantly higher in human muscle compared to C2C12 muscle constructs (unpaired t-test, p < 0.05). We are uncertain about the relevance of this finding, but it is likely an intrinsic feature related to the species since gender-specific differences have been found for this parameter in native mouse muscles ( Lafoux et al, 2020 ). Of note, this parameter is independent of CSA and provides a functional measurement that could be used to compare different studies regardless of the construct size or platform used.…”

The Pharmacokinetics of Butylscopolamine in Camel Plasma after Intravenous Administration

“…Appealing evidence shows that the TRPV1 channel plays key roles in thermosensation, oral sensation, proteasome activity, modulation of autophagy, energy homeostasis, muscle physiology, GI motility, and the release of inflammatory mediators as well as crosstalk between the immune system and sensory nervous system. 1,18- 24 In addition, the TRPV1 channel is involved in the modulation of synaptic transmission through pre-and post-synaptic mechanisms and microglia-to-neuron communication. 10 To elaborate, the TRPV1 channel modulates glutamatergic and GABAergic transmission and causes changes in neuronal firing.…”

“…8 Moreover, TRPV1 mutations are associated with muscle disorders such as exertional heat stroke and malignant hyperthermia. 24 Additionally, several studies have shown that TRPV1 activation leads to Ca 2+ release, membrane excitability, neurotransmitter release, and muscle contraction. 174 Supporting this contention, it has been revealed that the upregulation of nitric oxide and peroxynitrite in overloaded muscle activates the TRPV1 channel.…”

“…175 Also, TRPV1 knockout mice exhibited stronger muscles with improvement in neuromuscular function compared to wildtype counterparts. 24 In frogs, it was documented that TRPV1 activation decreased the tension of fast skeletal muscle fibers causing a change in muscle activity. 178 In addition, it was found that TRPV1 genetic deletion, inhibition, or desensitization in mice decreased the activity of osteoclasts in vitro and inhibited ovariectomy-induced bone loss as well as osteoporosis in vivo.…”