Functions of vacuolar H+-ATPases and voltage-gated proton channels coexisted in the plasma membrane of osteoclasts

破骨细胞在质膜上表达两种类型的电致H+选择性转运机制，即液泡H+-ATPases （V-ATPases）和电压门控质子通道。我们在全细胞钳形结构下对单细胞中的H+电流进行了鉴定，发现在生理细胞内pH值（>7.0）和膜电位（<-20 mV）下，V-ATPases占优势，但在高于激活阈值的电压下，通过H+通道的H+外排超过了V-ATPases，这表明这两种机制的作用转换很快。通过V-ATPases增加细胞内pH可抑制附近H+通道的激活，反之则无作用。细胞内pH值的升高，无论是由弱碱还是v - atp酶引起的，都促进了H+通道的动力依赖性内吞内化。这些数据提出了H+通道保留池的概念，并提出了破骨细胞中v - atp酶和H+通道相互作用的新机制。

Osteoclasts express two types of electrogenic H+-selective transport mechanisms at the plasma membrane, that is, vacuolar H+-ATPases (V-ATPases) and voltage-gated proton channels. Identifying these H+ currents in single cells under the whole-cell clamp configuration, we showed that V-ATPases were predominant at physiological intracellular pH (>7.0) and membrane potentials (<-20 mV), but that H+ efflux via the H+ channels exceeded those of V-ATPases at voltages higher than the activation threshold, suggesting that the two mechanisms switch their roles quickly. The increase in intracellular pH via V-ATPases inhibited activation of nearby H+ channels, but not vice versa. Elevation of intracellular pH, either by weak bases or V-ATPases, facilitated dynamin-dependent endocytic internalization of H+ channels. The data presented an idea of the reserving pool for H+ channels and suggested novel mechanisms for interaction between V-ATPases and H+ channels in osteoclasts.