Voltage-gated ion channels are transmembrane proteins in which at least one gate is controlled by the transmembrane potential. They are frequently ion specific and therefore selectively permeable to sodium (Nav channels), potassium (Kv channels), calcium (Cav channels) or chloride (CLC channels) ions. Depending on the channels, opening of the activation gate is triggered by membrane depolarization (e.g. Kv, Nav and Cav channels) or hyperpolarization (HCN channels for instance). In addition, in many voltage-gated channels, a so-called inactivation gate is also present. Compared to the activation gate, the latter is oppositely coupled to the potential: In Kv, Nav and Cav channels, upon membrane depolarization, the inactivation gate closes whereas the activation gate opens.
Various voltage-dependent channels have been identified, depending on the excitable cell types in which they are expressed and their physiological role. They are characterized by their conductance, ion selectivity, pharmacology and voltage-sensitivity. These properties are mainly dictated by the amino-acids sequence and structure of the pore forming subunit(s), the presence of accessory subunit(s), the membrane composition and the intra- and extracellular ions concentrations. Many mutations have been identified in these channels, impacting their functions and provoking diseases named channelopathies.
In 2012, we hosted a Research Topic on the
Molecular Mechanism of Voltage Dependency (with more than 100.000 views), bringing together scientists to collaborate and showcase the latest developments in the field.
Since our last Frontiers Research Topic, which was published as an e-Book too, the development of new approaches, such as the use of cryo-electron microscopy at the atomic scale and the original approach of split channels, to name a few, has led to a more precise understanding of the mechanisms of voltage-gating, their targeting by toxins, and also their physio-pathological implications. Given the wealth of recent electrophysiological, biochemical, optical, and structural data regarding ion channels voltage-dependence, there is clearly a need for putting together a new Research Topic/e-book, that would include up to date Reviews and Original Research describing molecular details of these complex voltage-gated channels function.