Voltage-Gated Ion Channels

PERMEATION MACHINERY OF GATED ION CHANNELS

Introduction:

Permeation means to pass through a pore, channel or a tube like structure and permeation machinery, a term attributed to overall structure of apparatus that is responsible for ion movement across plasma membrane. This apparatus involves channels that are commonly known as ion channels. Ion channels are pore-forming membrane proteins whose functions include establishing a resting membrane potential, shaping action potentials and other electrical signals by gating the flow of ions across the cell membrane, controlling the flow of ions across secretory and epithelial cells, and regulating cell volume. Ion channels are present in the membranes of all cells.

Structure of ion channels:

Channels

Any ion channel that opens and closes in response to changes in electrical potential across the cell membrane in which the channel is situated. There are several types of voltage-gated channel, each allowing the selective passage of a particular ion. Two types are especially important in transmitting action potentials along axons: voltage-gated sodium channels and voltage-gated potassium channels. The sodium channels open rapidly in response to initial depolarization of the axon plasma membrane, allowing sodium ions (Na+) to flood in. Depolarization also triggers less rapid opening of the potassium channels, which permits outflow of potassium ions (K+), thus acting to restore the membrane potential to its resting state. Voltage-dependent calcium channels also carry some of the depolarizing current in some cells. The sodium channel protein has positively charged voltage-sensing regions, which move towards negative charges on the outer surface of the membrane when the latter becomes depolarized. This opens the channel, allowing passage of sodium ions. Within a millisecond of channel opening, the voltage-sensing region returns to its original location, and a channel-inactivating segment moves to block the channel and allow the channel protein to revert to its resting

These channels are known mainly for their role in repolarizing the cell membrane following action potentials. The α subunits have six transmembrane segments, homologous to a single domain of the sodium channels. Correspondingly, they assemble as tetramers to produce a functioning channel.

Structure:

Typically, vertebrate voltage-gated K+ channels are tetramers of four identical subunits arranged as a ring, each contributing to the wall of the trans-membrane K+ pore. Each subunit is composed of six membrane spanning hydrophobic α-helical sequences. The high resolution crystallographic structure of the rat Kvα1.2/β2 channel has recently been solved

Selectivity:

Voltage-gated K+ channels are selective for K+ over other cations such as Na+. There is a selectivity filter at the narrowest part of the transmembrane pore.

Channel mutation studies have revealed the parts of the subunits that are essential for ion selectivity. They include the amino acid sequence (Thr-Val-Gly-Tyr-Gly) or (Thr-Val-Gly-Phe-Gly) typical to the selectivity filter of voltage-gated K+ channels. As K+ passes through the pore, interactions between potassium ions and water molecules are prevented and the K+ interacts with specific atomic components of the Thr-Val-Gly-[YF]-Gly sequences from the four channel subunits [1].

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