Characterization of Functional TRPV1 Channels in the Sarcoplasmic Reticulum of Mouse Skeletal Muscle

Abstract

TRPV1 represents a non-selective cation channel activated by capsaicin, acidosis and high temperature. In the central nervous system where TRPV1 is highly expressed, its physiological role in nociception is clearly identified. In skeletal muscle, TRPV1 appears implicated in energy metabolism and exercise endurance. However, how as a Ca2+ channel, it contributes to intracellular calcium concentration ([Ca2+]i) maintenance and muscle contraction remains unknown. Here, as in rats, we report that TRPV1 is functionally expressed in mouse skeletal muscle. In contrast to earlier reports, our analysis show TRPV1 presence only at the sarcoplasmic reticulum (SR) membrane (preferably at the longitudinal part) in the proximity of SERCA1 pumps. Using intracellular Ca2+ imaging, we directly accessed to the channel functionality in intact FDB mouse fibers. Capsaicin and resiniferatoxin, both agonists as well as high temperature (45°C) elicited an increase in [Ca2+]i. TRPV1-inhibition by capsazepine resulted in a strong inhibition of TRPV1-mediated functional responses and abolished channel activation. Blocking the SR release (with ryanodine or dantrolene) led to a reduced capsaicin-induced Ca2+ elevation suggesting that TRPV1 may participate to a secondary SR Ca2+ liberation of greater amplitude. In conclusion, our experiments point out that TRPV1 is a functional SR Ca2+ leak channel and may crosstalk with RyR1 in adult mouse muscle fibers.

Transient Receptor Potential Channels as Drug Targets: From the Science of Basic Research to the Art of Medicine

“…The literature is, however, confusing. Functional TRPV1 expression was reported in murine skeletal muscle (Lotteau et al, 2013) where capsaicin was noted to induce hypertrophy . In the perfused rat hind limb, RTX causes vasoconstriction and increased O 2 consumption (Eldershaw et al, 1994).…”

Capsaicin and N-Arachidonoyl-dopamine (NADA) Decrease Tension by Activating Both Cannabinoid and Vanilloid Receptors in Fast Skeletal Muscle Fibers of the Frog

“…A third possibility is capsaicin pretreatments, which activate TRPV1, may deplete Ca 2? stores (Lotteau et al 2013) resulting in reduced caffeine release and a consequent decline of contraction tension. In these experiments, pretreatment with capsaicin for 4 or 10 min does not significantly modify capsaicin's effects.…”

“…In neurons, the TRPV1 receptors are localized in the plasma membrane and in the SR (Olah et al 2001); in rat skeletal muscle, VR1 is expressed mainly in the SR (Xin et al 2005;Cavuoto et al 2007;Lotteau et al 2013). In these studies, the presence of VR1 mRNA was assessed in fast and slow skeletal muscle fibers from chicken, frog, and rat.…”

“…The vanilloid (capsaicin) receptor, VR1, has been described in rodent skeletal muscle; it is localized mainly in the sarcoplasmic reticulum (SR) (Xin et al 2005;Cavuoto et al 2007;Lotteau et al 2013). One agonist of VR1 is capsaicin, which is a vanilloid present in chili peppers (Szallasi and Blumberg, 1999;Vriens et al 2009).…”

Activation of Trpv1 by Nitric Oxide Donors Requires Co-Application of Sulfhydril-Containing Reagent

“…Transient Receptor Potential), в останні десятиріччя найбільш інтенсивно досліджувався як молекулярний сенсор високих температур у ноцицептивному діапазоні (більше ніж 42° С) і фармакологічна мішень капсаїцину, актив-ної речовини плодів червоного перцю роду Capsicum [10,11]. Окрім терморецептивних аферентних нейронів, ген TRPV1 також широко експресується в м'язовій, нервовій, епітеліальній та інших тканинах [12], при-чому може локалізуватися на субклітинному рівні як на плазматичній мембрані (зде-більшого в нейронах), так і на мембранах внутрішньоклітинних кальцієвих депо (зде-більшого в міоцитах) [13][14][15]. Відповідно до різноманіття функцій, до яких залучений TRPV1, він є виключно полімодальним біл-ком: до фізіологічних чинників його актива-ції на лежать, окрім високої температури, депо ля ризація мембрани, низький pH, а також низка міжклітинних трансмітерів і вторин-них посередників (наприклад, анандамід, N-арахідоноїлдопамін, деякі продукти лі-пок сигенази тощо) [10,11].…”