Water, proton transfer, and hydrogen bonding in ion channel gating

Several types of ion channels, the proteins responsible for the transport of ions across cell membranes, are described. Those of most interest are responsible for the functioning of nerve cells, and are voltage gated. Here, we propose a model for voltage gating that depends on proton transport. There are also channels that are proton-gated, of which some are bacterial. For one, a structure is known in the closed state, the KcsA channel (1). The proton gating of this channel suggests a part of the overall gating model we propose. Other bacterial channel structures are also known, but none that are relevant here, at least in one case because it appears to be in the open state. Voltage-gated channels of eukaryotes open in response to the depolarization of the membrane. It appears that there is some analogy in the structure of the voltage-gated channels to the structure of the smaller bacterial channels, including the one that is proton-gated. There is also significant experimental work in the literature on the nature of the gating current, a capacitative current that precedes the opening of the channel. The model we provide is based on the known properties of channels; in this model, voltage gating consists of three stages: first, the tunneling of a proton as depolarization begins, to initiate the sequence; second, proton transport along a sequence of (mostly) arginines, which is postulated to bring a proton to a critical gating region, where, third, a strong, short, hydrogen bond is weakened by the added proton, allowing the four domains to separate. The separation of the domains allows ions to pass through, and thus constitutes the opening of the channel. An analogy to the behavior of ferroelectrics is also described.