title: Effects of lactate on the voltage-gated sodium channels of rat skeletal muscle: modulating current opinion.
abstract: During muscle contraction, lactate production and translocation across the membrane increase. While it has recently been shown that lactate anion acts on chloride channel, less is known regarding a potential effect on the voltage-gated sodium channel (Na(v)) of skeletal muscle. The electrophysiological properties of muscle Na(v) were studied in the absence and presence of lactate (10 mM) by using the macropatch-clamp method in dissociated fibers from rat peroneus longus (PL). Lactate in the external medium (petri dish + pipette) increases the maximal sodium current, while the voltage dependence of activation and fast inactivation are shifted toward the hyperpolarized potentials. Lactate induces a leftward shift in the relationship between the kinetic parameters and the imposed potentials, resulting in an earlier recruitment of muscle Na(v). In addition, lactate significantly decreases the time constant of activation at voltages more negative than -10 mV, corresponding to an acceleration of Na(v) activation. The slow inactivation process is decreased by lactate, corresponding to an enhancement in the number of excitable Na(v). In an additional series of experiments, lactate (10 mM) was only added to the petri dish, while the pipette remained sealed on the membrane area. With this approach, the electrophysiological properties of Na(v) were unaffected by lactate compared with the control condition. Altogether, these data indicate that lactate modulates muscle Na(v) properties by an extracellular pathway. These effects are consistent with an enhancement in excitability, providing new insights into the role of lactate in muscle physiology.
authors.affiliation: Université de Brest, Faculté de Médecine et des Sciences de la Santé, EA 1274-M2S, Laboratoire de Physiologie, Brest, France.
authors.forename: F
authors.initials: F
authors.lastname: Rannou
authors.forename: R
authors.initials: R
authors.lastname: Leschiera
authors.forename: M A
authors.initials: MA
authors.lastname: Giroux-Metges
authors.forename: J P
authors.initials: JP
authors.lastname: Pennec
mesh_terms: D000818:Animals; D005260:Female; D015640:Ion Channel Gating; D007700:Kinetics; D019344:Lactic Acid / Q000378:metabolism*; D008564:Membrane Potentials; D009119:Muscle Contraction; D018482:Muscle, Skeletal / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000378:metabolism*; D015222:Sodium Channels / Q000378:metabolism*
chemical_list: D015222:Sodium Channels; D019344:Lactic Acid; D012964:Sodium