Structure and Function of Voltage-Gated Ion Channels Voltage-gated ion channels allow the flow of ions in response to changes in membrane voltage and are key elements in neuronal excitation and inhibition. Although ion channels can usually pass more than a single type of ion, voltage-gated channels are named according to the predominant ion that flows when the channel is open. Ion channels that are selective for Na+, K+, Ca2+, or Cl have been described in neuronal membranes. Certain ion channels that are gated directly by chemical neurotransmitters such as glutamate and acetylcholine are selective for Na+, K+, and Ca2+ but exclude Cl and are called nonselective cationic channels.
[...] Cloning studies of channels from Shaker indicate that some channels, like Na+ channels, are proteins that have six putative membrane spanning regions (S1 through a reentrant p loop between S5 and S6 that lines the ion channel pore, and a voltage sensor in the S4 region. These channel proteins are only about one fourth the size of the Na+ channel a-subunit and have only one of the homologous internal repeats seen in Na+ channels. It also appears that there are multiple distinct subfamilies of channels based on genetic studies in Drosophila, where the most detailed analysis has been done. [...]
[...] Some ion channels are opened by hyperpolarization instead of depolarization. These include anomalous (inward) rectifier and H channels that allow to enter rather than exit the cell. The name “anomalous rectifier” (also called “inward rectifier”) indicates that, in contrast to the delayer rectifier, this channel passes much better in an inward than in an outward direction. The anomalous rectifier and H channels (hyperpolarization activated channels) are believed to contribute to the neuronal resting membrane potential and to pacemaker firing in certain neurons. [...]
[...] primary protein structure and ion channel function in Na+ channels have been examined using mutations of specific amino acid residues. It appears that both the amino- and carboxy-terminals of the subunits are located intracellularly. The fourth membrane spanning region plays a key role in sensing the transmembrane voltage changes that allow channel gating. Between the S5 and S6 membrane spanning regions there is a segment of hydrophobic amino acids that does not completely cross the lipid membrane bilayer. This reentrant loop of amino acids (called a p loop) is a feature shared by other voltage-gated ion channels and appears to form the lining of the ion channel pore. [...]
[...] These cyclic- nucleotide gated (CNG) channels have structural features that are reminiscent of voltage-gated calcium channels, including the presence of six membrane spanning regions and a p-loop that lines the ion channel. CNG channels are nonselectively permeable to cations, but like voltage-gated calcium channels, the flow of monovalent cations through CNG channels is blocked by calcium. Chloride Channels In most neurons, is present at higher concentrations extracellularly than intracellularly and the equilibrium potential fo r is near the cell resting membrane potential. [...]
[...] These channels consist of five distinct subunits that are termed a1 (165–195 kDa), a2/d (~170 kDa), b kDa), and g kDa). The a1-subunits show considerable sequence homology percent) to voltage-gated Na+ channels and form the ion channel pore. A recurring theme in the a1-subunits is the existence of four homologous internal repeats that each contain six putative membrane spanning regions and a p-loop. HVA a1 Ca2+ channel subunits contain the dihydropyridine binding site and show structural heterogeneity, with current evidence suggesting the existence of several different a1 subunits (designated a1A-E). [...]
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