Chapter 3.7 - Voltage gated proton channel (Hv1)

Abstract

The voltage-gated proton channel (Hv1) is a highly selective channel that only allows the flow for one ion: H+ (protons). It is activated by membrane depolarization and pH gradient. An increased external and decreased internal pH opens the Hv1 channel, according to all the publications. This is exactly the opposite of what happens in cancer where pHi is high and pHe is low. Extrusion of protons by Hv1 follows the concentration gradient. In normal cells with a lower intracellular pH and a higher extracellular pH, the extrusion of protons is easily understandable, because the concentration is lower outside the cell. On the other hand, the inverted pH gradient in cancer represents a conundrum of how Hv1 functions. The voltage gated proton channels have been neglected as pHtome participants. There is abundant evidence of Hv1 role in cancer progression. Hv1 in cancer is deregulated and exports protons even with a high intracellular pH, thus participating in the pH gradient inversion. This channel works in close association with NADPH oxidase 2.