S1P 3 receptor influences key physiological properties of fast-twitch extensor digitorum longus muscle

• Published in: Journal of applied physiology (1985) Vol. 120; no. 11; pp. 1288 - 1300
• Main Authors: Germinario, Elena, Bondì, Michela, Cencetti, Francesca, Donati, Chiara, Nocella, Marta, Colombini, Barbara, Betto, Romeo, Bruni, Paola, Bagni, Maria Angela, Danieli-Betto, Daniela
• Format: Journal Article
• Language: English
• Published: 01.06.2016
• ISSN: 8750-7587; 1522-1601
• DOI: 10.1152/japplphysiol.00345.2015

To examine the role of sphingosine 1-phosphate (S1P) receptor 3 (S1P 3 ) in modulating muscle properties, we utilized transgenic mice depleted of the receptor. Morphological analyses of extensor digitorum longus (EDL) muscle did not show evident differences between wild-type and S1P 3 -null mice. The body weight of 3-mo-old S1P 3 -null mice and the mean cross-sectional area of transgenic EDL muscle fibers were similar to those of wild-type. S1P 3 deficiency enhanced the expression level of S1P 1 and S1P 2 receptors mRNA in S1P 3 -null EDL muscle. The contractile properties of S1P 3 -null EDL diverge from those of wild-type, largely more fatigable and less able to recover. The absence of S1P 3 appears responsible for a lower availability of calcium during fatigue. S1P supplementation, expected to stimulate residual S1P receptors and signaling, reduced fatigue development of S1P 3 -null muscle. Moreover, in the absence of S1P 3 , denervated EDL atrophies less than wild-type. The analysis of atrophy-related proteins in S1P 3 -null EDL evidences high levels of the endogenous regulator of mitochondria biogenesis peroxisome proliferative-activated receptor-γ coactivator 1α (PGC-1α); preserving mitochondria could protect the muscle from disuse atrophy. In conclusion, the absence of S1P 3 makes the muscle more sensitive to fatigue and slows down atrophy development after denervation, indicating that S1P 3 is involved in the modulation of key physiological properties of the fast-twitch EDL muscle.