NOX Family NADPH Oxidases

Open Access
Publisher Website
Google Scholar
Abstract
20 yr ago, Thomas and Meech (1982) described the first voltage-activated proton currents in the plasma membrane of eukaryotic cells, the currents that are the focus of this perspective. These first recordings were performed in neurons from the snail Helix Stagnalis. Since then, similar currents have been observed in a variety of cells from different phyla, including mammalian and human cells (for review see Eder and DeCoursey, 2001). The unique features of the currents led to numerous speculations as to the nature of the underlying transport protein. For years, it was prudently referred to as “proton conductance,” before the term “channel” became generally accepted. Like typical ion channels, proton channels do not require ATP or coupling to other ions and exhibit complex gating properties. Unlike typical ion channels however, protons channels are markedly temperature dependent, (Q10 = 10 in the range 24–36°C) (Kuno et al., 1997), nearly perfectly selective for H+ over other ions (pH/px > 106), and their unitary conductance, estimated from noise analysis, is in the fS range (Bernheim et al., 1993). These unusual properties, as well as the unique way by which protons can move in water and across membrane proteins, suggest that the underlying transport system is not a water-filled pore, and thus not a channel according to its classical definition. The H+ transport protein is therefore most likely structurally unrelated to classical ion channels. For this reason, attempts to clone the channel by homology have proven unsuccessful, and the lack of high-affinity pharmacological tools has further hampered their molecular identification. Based on the electrophysiological and pharmacological characteristics, it is likely that there are different types of H+ channels, not only in different cell types (DeCoursey, 1998), but even within a given cell type (Banfi et al., 1999).