Mediates voltage-dependent potassium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a potassium-selective channel through which potassium ions may pass in accordance with their electrochemical gradient. The channel activity is up-regulated by cAMP.
Am. J. Physiol. Renal Physiol. 278, F1013-21-F1013-21 (2000)[PubMed:10836990]
Our laboratory previously cloned a novel rabbit gene (Kcn1), expressed in kidney, heart, and aorta, and predicted to encode a protein with 58% amino acid identity with the K channel Shaker Kv1.3 (Yao X et al. Proc Natl Acad Sci USA 92: 11711-11715, 1995). Because Kcn1 did not express well (peak current in Xenopus laevis oocytes of 0.3 microA at +60 mV), the human homolog (KCNA10) was isolated, and its expression was optimized in oocytes. KCNA10 mediates voltage-gated K(+) currents that exhibit minimal steady-state inactivation. Ensemble currents of 5-10 microA at +40 mV were consistently recorded from injected oocytes. Channels are closed at the holding potential of -80 mV but are progressively activated by depolarizations more positive than -30 mV, with half-activation at +3.5 +/- 2.5 mV. The channel displays an unusual inhibitor profile because, in addition to being blocked by classical K channel blockers (barium tetraethylammonium and 4-aminopyridine), it is also sensitive to inhibitors of cyclic nucleotide-gated (CNG) cation channels (verapamil and pimozide). Tail-current analysis shows a reversal potential shift of 47 mV/decade change in K concentration, indicating a K-to-Na selectivity ratio of at least 15:1. The phorbol ester phorbol 12-myristate 13-acetate, an activator of protein kinase C, inhibited whole cell current by 42%. Analysis of single-channel currents reveals a conductance of approximately 11 pS. We conclude KCNA10 is a novel human voltage-gated K channel with features common to both K-selective and CNG cation channels. Given its distribution in renal blood vessels and heart, we speculate that KCNA10 may be involved in regulating the tone of renal vascular smooth muscle and may also participate in the cardiac action potential.
Catalysis of the transmembrane transfer of a potassium ion by a delayed rectifying voltage-gated channel. A delayed rectifying current-voltage relation is one where channel activation kinetics are time-dependent, and activation is slow.
Catalysis of the transmembrane transfer of a cation by a channel that opens when intracellular cyclic nucleotide has been bound by the channel complex or one of its constituent parts.
Potassium (K) channels are important components of virtually all cells, and they play critical roles in many cellular functions. KCNA10 represents a new class of K channel specifically regulated by cGMP and postulated to mediate the effects of substances that increase intracellular cGMP. Since KCNA10 has the potential to be useful in candidate gene analysis of inherited diseases, the human gene for KCNA10 was characterized. Fluorescence in situ hybridization indicates that human KCNA10 maps to chromosome 1 at p13.1-->p22.1. Finer mapping of the gene was achieved by PCR of a set of CEPH YAC clones that spanned the region of interest. We found that YAC 818b9 contains human KCNA10. These data indicate human KCNA10 maps to 1p13.1 and resides within the genetic interval defined by microsatellite loci D1S2809 and D1S2726. That region of chromosome 1 contains another K channel gene, KCNA3.
Potassium (K) channels are important components of virtually all cells, and they play critical roles in many cellular functions. KCNA10 represents a new class of K channel specifically regulated by cGMP and postulated to mediate the effects of substances that increase intracellular cGMP. Since KCNA10 has the potential to be useful in candidate gene analysis of inherited diseases, the human gene for KCNA10 was characterized. Fluorescence in situ hybridization indicates that human KCNA10 maps to chromosome 1 at p13.1-->p22.1. Finer mapping of the gene was achieved by PCR of a set of CEPH YAC clones that spanned the region of interest. We found that YAC 818b9 contains human KCNA10. These data indicate human KCNA10 maps to 1p13.1 and resides within the genetic interval defined by microsatellite loci D1S2809 and D1S2726. That region of chromosome 1 contains another K channel gene, KCNA3.
The process of creating protein oligomers, compounds composed of a small number, usually between three and ten, of identical component monomers. Oligomers may be formed by the polymerization of a number of monomers or the depolymerization of a large protein polymer.
IEAInterPro 2 GO
Pathways
According to Reactome, this protein belongs to the following pathway:
Protein involved in the transport of ions. Such proteins are usually transmembrane and mediate a movement of ions across cell membranes. Transport may be passive (facilitated diffusion; down the electrochemical gradient), or active (against the electrochemical gradient). Active transport requires energy which may come from light, oxidation reactions, ATP hydrolysis, or cotransport of other ions or molecules.
Protein involved in the transport of a molecule (metabolite, protein, etc), a ion or an electron across cell membranes, inside the cell or in a tissue fluid.
Protein which is part of a transmembrane protein complex that forms a hydrophilic channel across the lipid bilayer through which specific inorganic ions can diffuse down their electrochemical gradients. The channels are usually gated and only open in response to a specific stimulus, such as a change in membrane potential (voltage-gated) or the binding of a ligand (ligand-gated channel).
Protein which is part of a transmembrane protein complex that forms a hydrophilic channel across the lipid bilayer through which potassium ions can diffuse down their electrochemical gradient. The channels are gated and only open in response to a specific stimulus, such as a change in membrane potential (voltage-gated). They are important for the regulation of the resting membrane potential and for the control of the shape and frequency of action potentials.
Protein which is a component of a voltage-gated channel. Voltage-gated ion channels are responsible for the electrical activity in a variety of cell types. They probably exist in all life forms.
A reference proteome is a set of protein sequences derived from a complete proteome which constitutes a defined standard for a particular user community. Reference proteomes are manually defined according to a number of criteria. They cover the proteomes of well- studied model organisms and other proteomes of interest for biomedical and biotechnological research. Reference proteomes have been selected to provide broad coverage of the tree of life, and constitute a representative cross-section of the taxonomic diversity to be found within UniProtKB.
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