Biophysical properties of the voltage‐gated proton channel H_V1

Abstract

The biophysical properties of the voltage gated proton channel (HV1) are the key elements of its physiological function. The voltage gated proton channel is a unique molecule that in contrast to all other ion channels is exclusively selective for protons. Alone among proton channels, it has voltage and time dependent gating like other “classical” ion channels. HV1 is furthermore a sensor for the pH in the cell and the surrounding media. Its voltage dependence is strictly coupled to the pH gradient across the membrane. This regulation restricts opening of the channel to specific voltages at any given pH gradient, therefore allowing HV1 to perform its physiological task in the tissue it is expressed in. For HV1 there is no known blocker. The most potent channel inhibitor is zinc (Zn2+) which prevents channel opening. An additional characteristic of HV1 is its strong temperature dependence of both gating and conductance. In contrast to single-file water filled pores like the gramicidin channel, HV1 exhibits pronounced deuterium effects and temperature effects on conduction, consistent with a different conduction mechanism than other ion channels. These properties may be explained by the recent identification of an aspartate in the pore of HV1 that is essential to its proton selectivity.

Voltage-Gated Proton Channels: Molecular Biology, Physiology, and Pathophysiology of the HVFamily

“…Recent reviews, most of which focus on more restricted areas than the present one, include References 62, 102, 103, 105, 106, 110, 123, 143, 254, 302, 354, 496. A series of focused reviews on proton channels is available online in Wiley Interdisciplinary Reviews: Membrane Transport and Signaling (60, 121, 156, 323, 357, 420). …”

Consequences of Dimerization of the Voltage-Gated Proton Channel

“…Is it possible that enhanced gating reflects conversion of the normally dimeric hH V 1 to monomeric status? This suggestion [3] has not yet been resolved beyond doubt, but the bulk of evidence suggests that this is not the case [77]. …”

Zinc Nutrition and Inflammation in the Aging Retina

“…Zinc can either participate, directly, in chemical catalysis or, indirectly, by maintaining protein structure or stability. For this reason, it has an important regulatory role in a wide variety of biological processes, acting as a catalyst for more than 300 enzymes and is contained within thousands of proteins, as a zinc finger domain . Zinc plays a key role in fundamental cellular processes such as DNA synthesis, RNA transcription, cell division, and activation, as well as in prevention of cell apoptosis .…”

“…For this reason, it has an important regulatory role in a wide variety of biological processes, acting as a catalyst for more than 300 enzymes and is contained within thousands of proteins, as a zinc finger domain. [29][30][31][32][33][34][35][36][37][38][39][40][41] Zinc plays a key role in fundamental cellular processes such as DNA synthesis, RNA transcription, cell division, and activation, [42] as well as in prevention of cell apoptosis. [43] It also has a significant role in affecting signal transduction for cellular function, [44] in particular for the development and integrity of the immune system, affecting both innate and adaptive immune responses, which represent non-specific or specific responses, respectively, to foreign macromolecules (antigens).…”