KCNA1

This gene encodes a voltage-gated delayed potassium channel that is phylogenetically related to the Drosophila Shaker channel. The encoded protein has six putative transmembrane segments (S1-S6), and the loop between S5 and S6 forms the pore and contains the conserved selectivity filter motif (GYGD). The functional channel is a homotetramer. The N-terminus of the channel is associated with beta subunits that can modify the inactivation properties of the channel as well as affect expression levels. The C-terminus of the channel is complexed to a PDZ domain protein that is responsible for channel targeting. Mutations in this gene have been associated with myokymia with periodic ataxia (AEMK).

potassium voltage-gated channel subfamily A member 1

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 (PubMed:19903818).
Contributes to the regulation of the membrane potential and nerve signaling, and prevents neuronal hyperexcitability (PubMed:17156368).
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 (PubMed:19912772).
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 (PubMed:12077175, PubMed:17156368).
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 (PubMed:12077175, PubMed:17156368).
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 (PubMed:19912772, PubMed:19968958, PubMed:19307729, PubMed:19903818).
In contrast, a heterotetrameric channel formed by KCNA1 and KCNA4 shows rapid inactivation (PubMed:17156368).
Regulates neuronal excitability in hippocampus, especially in mossy fibers and medial perforant path axons, preventing neuronal hyperexcitability. Response to toxins that are selective for KCNA1, respectively for KCNA2, suggests that heteromeric potassium channels composed of both KCNA1 and KCNA2 play a role in pacemaking and regulate the output of deep cerebellar nuclear neurons (By similarity).
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 (By similarity).
Required for normal neuromuscular responses (PubMed:11026449, PubMed:17136396).
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 (By similarity).
Required for normal responses to auditory stimuli and precise location of sound sources, but not for sound perception (By similarity).
The use of toxins that block specific channels suggest that it contributes to the regulation of the axonal release of the neurotransmitter dopamine (By similarity).
Required for normal postnatal brain development and normal proliferation of neuronal precursor cells in the brain (By similarity).
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 (PubMed:23903368, PubMed:19307729).

Cell communication by electrical couplingISS:UniProtKB
Cellular protein localizationIEA:Ensembl
Cellular response to magnesium ionISS:UniProtKB
Chemical synaptic transmissionManual Assertion Based On ExperimentTAS:ProtInc
Detection of mechanical stimulus involved in sensory perception of painISS:UniProtKB
Detection of mechanical stimulus involved in sensory perception of touchISS:UniProtKB
Hippocampus developmentIEA:Ensembl
Magnesium ion homeostasisManual Assertion Based On ExperimentIMP:UniProtKB
Neuroblast proliferationIEA:Ensembl
Neuromuscular processManual Assertion Based On ExperimentIMP:UniProtKB
Neuronal action potentialISS:UniProtKB
Neuronal signal transductionISS:UniProtKB
Positive regulation of voltage-gated potassium channel activityIEA:Ensembl
Potassium ion transmembrane transportManual Assertion Based On ExperimentIMP:UniProtKB
Potassium ion transportManual Assertion Based On ExperimentTAS:ProtInc
Protein homooligomerizationIEA:InterPro
Regulation of membrane potentialManual Assertion Based On ExperimentIMP:UniProtKB
Regulation of muscle contractionISS:UniProtKB
Startle responseIEA:Ensembl

Cell membrane; Membrane; Cell projection, axon; Cytoplasmic vesicle; Perikaryon; Endoplasmic reticulum; Cell projection, dendrite; Cell junction; Cell junction, synapse; Cell junction, synapse, presynaptic cell membrane; Cell junction, synapse, presynapse. Homotetrameric KCNA1 is primarily located in the endoplasmic reticulum. Interaction with KCNA2 and KCNAB2 or with KCNA4 and KCNAB2 promotes expression at the cell membrane (By similarity).

Episodic ataxia 1 (EA1):
An autosomal dominant disorder characterized by brief episodes of ataxia and dysarthria. Neurological examination during and between the attacks demonstrates spontaneous, repetitive discharges in the distal musculature (myokymia) that arise from peripheral nerve. Nystagmus is absent.
Myokymia isolated 1 (MK1):
A condition characterized by spontaneous involuntary contraction of muscle fiber groups that can be observed as vermiform movement of the overlying skin. Electromyography typically shows continuous motor unit activity with spontaneous oligo- and multiplet-discharges of high intraburst frequency (myokymic discharges). Isolated spontaneous muscle twitches occur in many persons and have no grave significance.

Cytoplasmic: 1-164
Helical: 165-186
Extracellular: 187-220
Helical: 221-242
Cytoplasmic: 243-253
Helical: 254-274
Extracellular: 275-287
Helical: 288-308
Cytoplasmic: 309-323
Helical: 324-345
Extracellular: 346-359
Helical: 360-379
Extracellular: 380-386
Helical: 387-415
Cytoplasmic: 416-495

N-glycosylated.By Similarity
Palmitoylated on Cys-243; which may be required for membrane targeting.
Phosphorylated on tyrosine residues. Phosphorylation increases in response to NRG1; this inhibits channel activity (By similarity).
Phosphorylation at Ser-446 regulates channel activity by down-regulating expression at the cell membrane (PubMed:23774215).