Protein Details: Potassium voltage-gated channel subfamily A member 1
Protein ID
ICDB_Pro_0359
Protein Name
Potassium voltage-gated channel subfamily A member 1
Gene Name
Kcna1
Organism
Mus musculus (Mouse)
Length
495 amino acids
AlphaFoldDB
AF-P16388-F1-model_v4.pdb
Function
Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes; primarily in the brain and the central nervous system; but also in the kidney. Contributes to the regulation of the membrane potential and nerve signaling; and prevents neuronal hyperexcitability . Forms tetrameric potassium-selective channels through which potassium ions pass in accordance with their electrochemical gradient. The channel alternates between opened and closed conformations in response to the voltage difference across the membrane. Can form functional homotetrameric channels and heterotetrameric channels that contain variable proportions of KCNA1; KCNA2; KCNA4; KCNA5; KCNA6; KCNA7; and possibly other family members as well; channel properties depend on the type of alpha subunits that are part of the channel. Channel properties are modulated by cytoplasmic beta subunits that regulate the subcellular location of the alpha subunits and promote rapid inactivation of delayed rectifier potassium channels. In vivo; membranes probably contain a mixture of heteromeric potassium channel complexes; making it difficult to assign currents observed in intact tissues to any particular potassium channel family member. Homotetrameric KCNA1 forms a delayed-rectifier potassium channel that opens in response to membrane depolarization; followed by slow spontaneous channel closure . In contrast; a heterotetrameric channel formed by KCNA1 and KCNA4 shows rapid inactivation (By similarity). Regulates neuronal excitability in hippocampus; especially in mossy fibers and medial perforant path axons; preventing neuronal hyperexcitability. May function as down-stream effector for G protein-coupled receptors and inhibit GABAergic inputs to basolateral amygdala neurons (By similarity). May contribute to the regulation of neurotransmitter release; such as gamma-aminobutyric acid (GABA) release (By similarity). Plays a role in regulating the generation of action potentials and preventing hyperexcitability in myelinated axons of the vagus nerve; and thereby contributes to the regulation of heart contraction . Required for normal neuromuscular responses. Regulates the frequency of neuronal action potential firing in response to mechanical stimuli; and plays a role in the perception of pain caused by mechanical stimuli; but does not play a role in the perception of pain due to heat stimuli. Required for normal responses to auditory stimuli and precise location of sound sources; but not for sound perception . The use of toxins that block specific channels suggest that it contributes to the regulation of the axonal release of the neurotransmitter dopamine. Required for normal postnatal brain development and normal proliferation of neuronal precursor cells in the brain . Plays a role in the reabsorption of Mg(2+) in the distal convoluted tubules in the kidney and in magnesium ion homeostasis; probably via its effect on the membrane potential (By similarity)
Sequence
PDB Structures
Ligand Binding
Binding Site
Disease
Location
Detected in brain (PubMed:21483673; PubMed:22158511; PubMed:2451788; PubMed:9581771). Expressed in cerebellar cortex basket cell terminals; the area surround the Purkinje cell soma; and the pinceaux expansions encircling the axon initial segment (at protein level) (PubMed:26269648). Detected in the juxtaparanodal regions of the nodes of Ranvier in myelinated axons (PubMed:8046438; PubMed:8361541). Detected in the paranodal region in sciatic nerve (PubMed:9736643). Detected on cell bodies in cerebellum; dorsal and ventral cochlear nucleus; pontine reticular nucleus; mesencephalic trigeminal nucleus; motor trigeminal nucleus and the pricipal sensory trigeminal nucleus (PubMed:8046438). Detected in terminal fields of basket cells in the cerebellum corpus medullare (PubMed:8046438; PubMed:8361541; PubMed:9581771). Detected in hippocampus CA3 pyramidal neurons and in the hilus and stratum moleculare of the dentate gyrus (PubMed:14686897; PubMed:8046438; PubMed:9581771). Detected in the central nucleus and the external nucleus of the inferior colliculus (PubMed:21966978; PubMed:8046438). Detected in fiber tracts in the optic tract; external medullary lamina; stria terminalis; medulla; ventral pallidum and substantia nigra (PubMed:8046438). Detected in neurons from dorsal root ganglion (PubMed:23473320). Detected in neurons in the medial nucleus of the trapezoid body (PubMed:12611922). Detected in midbrain dopamine neuron axon terminals (PubMed:21233214). Detected in brain cortex (PubMed:14686897; PubMed:8046438). Detected in brainstem (PubMed:8361541). Detected in juxtaparanodal regions of the nodes of Ranvier in the vagus nerve; but only at very low levels in the heart (PubMed:20392939; PubMed:22641786). Detected in the islet of Langerhans (PubMed:21483673). Detected at the luminal membrane in distal convoluted tubules in the kidney (at protein level) (PubMed:19307729). Detected in hippocampus; thalamus; neocortex and ventral brain cortex; including the piriform and entorhinal cortex and the amygdala (PubMed:14686897). Detected in midbrain dopamine neurons (PubMed:21233214). Detected in heart atrium; ventricle; sinoatrial node and atrioventricular node (PubMed:20392939).
DOI ID
10.1126/science.2305265; 10.1038/332837a0; 10.1038/365075a0; 10.1523/jneurosci.14-08-04588.1994; 10.1007/s003359900259; 10.1523/jneurosci.18-18-07200.1998; 10.1016/s0896-6273(00)81018-1; 10.1523/jneurosci.19-08-02852.1999; 10.1111/j.1460-9568.2003.03044.x; 10.1113/jphysiol.2002.035568; 10.1126/science.1086763; 10.1038/nsmb825; 10.1074/mcp.t500041-mcp200; 10.1186/1471-2202-8-10; 10.1002/hipo.20268; 10.1007/s12035-007-8001-0; 10.1172/jci36948; 10.1016/j.cell.2010.12.001; 10.1523/jneurosci.5591-09.2010; 10.1111/j.1460-9568.2011.07834.x; 10.1074/jbc.m110.153262; 10.1371/journal.pone.0018213; 10.1523/jneurosci.1958-11.2012; 10.1113/jphysiol.2012.228486; 10.1113/jphysiol.2012.235606; 10.1038/nn.3006; 10.1016/j.nbd.2013.02.009; 10.1016/j.neuron.2012.12.035; 10.1111/epi.12793; 10.1038/ki.2013.280; 10.1523/jneurosci.1346-15.2015
RefSeq
NP_034725.3