Mammalian skeletal muscle does not express functional voltage-gated H+ channels

High metabolic activity and existence of a large transmembrane inward electrochemical gradient for H + at rest promote intracellular acidification of skeletal muscle. Exchangers and cotransports efficiently contend against accumulation of intracellular H + and associated deleterious effects on muscle functions. Voltage-gated H + channels have also been found to represent another H + extrusion pathway in cultured muscle cells. Up to now, the skeletal muscle cell was therefore the unique vertebrate excitable cell in which voltage-gated H + currents have been described. In this study, we show that, unlike cultured cells, single mouse muscle fibers do not generate H + currents in response to depolarization. In contrast, expression of human voltage-gated H + channels in mouse muscle gives rise to robust outward voltage-gated H + currents. This result excludes that inappropriate experimental conditions may have failed to reveal voltage-gated H + currents in control muscle. This work therefore demonstrates that fully differentiated mammalian muscle fibers do not express functional voltage-gated H + channels and consequently can no longer be considered as the only vertebrate excitable cells exhibiting voltage-gated H + currents.