A Voltage-gated H(+) Channel is a Powerful Mechanism for pH Homeostasis in Murine Osteoclasts

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Osteoclasts secrete a large amount of proton (H+) ions and proteolytic enzymes intobone resorption pit to degrade bone matrix. In addition to H+ pumps and exchangers,voltage-gated H+ channels, which are H+ conductive pathways, are expressed inosteoclasts. H+ channels are distinct in their strong H+ extrusion ability, but thefunctional role is not clear. This is the first study of H+ channels in murine osteoclastsgenerated from mononuclear precursors in the presence of a soluble form of receptoractivator of nuclear factor kappa B ligand (RANKL) and macrophage colonystimulating factor (M-CSF). The H+ channel was characterized by voltage- andpH-dependent activation, slow activation kinetics, and outward rectification. Thereversal potential (Vrev) was shifted to more positive potentials by decreasing the pHgradient across the plasma membrane (ΔpH). Employing Vrev as a real time monitor ofpH in clamped cells, it is revealed that the H+ channel activation could decrease ΔpH by~0.43 unit/s. Decline in the current during prolonged depolarizations was accompaniedby a positive shift in Vrev. This implies that the H+ channel activity is auto-regulated bysensing ΔpH, to compensate for pH imbalance. The H+ current-density in cells with ≥6nuclei was significantly smaller than that in cells with ≤5 nuclei, although the activationrate was unaltered. Thus, the H+ channel activity may alter during osteoclastogenesis.These data suggest the H+ channel is a powerful mechanism for pH homeostasis ofosteoclasts that are exposed to drastic change in pH environments during the boneresorption cycle.

A Voltage-gated H(+) Channel is a Powerful Mechanism for pH Homeostasis in Murine Osteoclasts

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