Effects of sphingosine 1-phosphate on excitation–contraction coupling in mammalian skeletal muscle

Abstract

Sphingosine 1-phosphate (S1P) activates a subset of plasma membrane receptors of the endothelial differentiation gene family (EdgRs) in many cell types. In C2C12 myoblasts, exogenous S1P elicits Ca2+ transients by activating voltage-independent plasma membrane Ca2+ channels and intracellular Ca2+-release channels. In this study, we investigated the effects of exogenous S1P on voltage-dependent L-type Ca2+ channels in skeletal muscle fibers from adult mice. To this end, intramembrane charge movements (ICM) and L-type Ca2+ current (I(Ca)) were measured in single cut fibers using the double Vaseline-gap technique. Our data showed that submicromolar concentrations of S1P (100 nM) caused a approximately 10-mV negative shift of the voltage threshold and transition voltages of q(gamma) and q(h) components of ICM, and of I(Ca) activation and inactivation. Biochemical studies showed that EdgRs are expressed in skeletal muscles. The involvement of EdgRs in the above S1P effects was tested with suramin, a specific inhibitor of Edg-3Rs. Suramin (200 microM) significantly reduced, by approximately 90%, the effects of S1P on ICM and I(Ca), suggesting that most of S1P action occurred via Edg-3Rs. Moreover, SIP at concentration above 10 microM elicited intracellular Ca2+ transients in muscle fibers loaded with the fluorescent Ca2+ dye Fluo-3, as detected by confocal laser scanning microscopy.

Neuronal differentiation of human mesenchymal stem cells: Changes in the expression of the Alzheimer's disease-related gene seladin-1

“…These channels were very likely of neuronal type, as suggested by additional experiments indicating that T-and HVA-Ca 2+ channels of neuronal phenotype were expressed. Notably, these Ca 2+ currents are those reported in neurons [44,45], whereas cardiac and skeletal muscle express T and L-type channels with different properties [46,47]. With regard to the Na + current, Boltzmann parameters were also consistent with those found in differentiated neurons [48,49] and differed from those observed in cardiac and skeletal muscle cells [50].…”

Sphingosine-1-phosphate: distribution, metabolism and role in the regulation of cellular functions

“…S1P receptors have been detected in skeletal muscle [117]. A S1P signaling pathway via S1P(2)R and activation of ERK1/ERK2 and p38 MAPK appeared to be important for the suppression of cell proliferation and stimulation of myogenic differentiation [118].…”

Excitation-contraction coupling and mechano-sensitivity in denervated skeletal muscles

“…In particular, the qγ movement triggers the opening of the coupled RyRs/CRCs, allowing a high Ca 2+ flux from the SR into the myoplasm and promoting muscle contraction. The qh charge mobilization move slower than qγ and determines the opening of the sarcolemmal L-CaC that allows Ca [11,45]. However, in all the models the charge particles involved in the opening of L-CaC move coordinately because of the interaction between them.…”

“…For example, insulin-like growth factor 1 (IGF-1) splicing variants produced by muscle cells are upregulated during muscle hypertrophy induced by overload, stretch or stretch combined with electrical stimulation. Another autocrine-paracrine growth factor is sphingosine 1-phosphate, S1P [11,16,23,24,70]. Finally, there are locally generated negative regulators of muscle functions as IL-1, IL-6 and TNF-α.…”

“…When the TT is depolarized by the action potential the charged S4-segment senses the new potential and moves. In fact, in normally polarized skeletal muscle fibers, ICM has been resolved into three components, an early qß, evoked by any depolarizing step, and two delayed components, qγ and qh [11,21] evoked only by voltage steps more positive than a certain threshold (about -56 and -38 mV in frog and rat, respectively). The time course of qß shows a monotonic decay and it seems not to be involved in ECC since the total amount of charge moved is not affected by pharmacological interventions directed at L-CaC such as Cd 2+ , nifedipine or alkanols.…”