KCNMA1

MaxiK channels are large conductance, voltage and calcium-sensitive potassium channels which are fundamental to the control of smooth muscle tone and neuronal excitability. MaxiK channels can be formed by 2 subunits: the pore-forming alpha subunit, which is the product of this gene, and the modulatory beta subunit. Intracellular calcium regulates the physical association between the alpha and beta subunits. Alternatively spliced transcript variants encoding different isoforms have been identified.

Full Name

Potassium Calcium-Activated Channel Subfamily M Alpha 1

Function

Potassium channel activated by both membrane depolarization or increase in cytosolic Ca(2+) that mediates export of K(+) (PubMed:29330545, PubMed:31152168).
It is also activated by the concentration of cytosolic Mg(2+). Its activation dampens the excitatory events that elevate the cytosolic Ca(2+) concentration and/or depolarize the cell membrane. It therefore contributes to repolarization of the membrane potential. Plays a key role in controlling excitability in a number of systems, such as regulation of the contraction of smooth muscle, the tuning of hair cells in the cochlea, regulation of transmitter release, and innate immunity. In smooth muscles, its activation by high level of Ca(2+), caused by ryanodine receptors in the sarcoplasmic reticulum, regulates the membrane potential. In cochlea cells, its number and kinetic properties partly determine the characteristic frequency of each hair cell and thereby helps to establish a tonotopic map. Kinetics of KCNMA1 channels are determined by alternative splicing, phosphorylation status and its combination with modulating beta subunits. Highly sensitive to both iberiotoxin (IbTx) and charybdotoxin (CTX).

Biological Process

Cellular potassium ion homeostasisManual Assertion Based On ExperimentIDA:UniProtKB
MicturitionManual Assertion Based On ExperimentIDA:UniProtKB
Negative regulation of cell volumeManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of apoptotic processManual Assertion Based On ExperimentIMP:UniProtKB
Potassium ion transportManual Assertion Based On ExperimentIDA:UniProtKB
Regulation of ion transmembrane transportIEA:UniProtKB-KW
Regulation of membrane potentialManual Assertion Based On ExperimentIDA:UniProtKB
Relaxation of vascular associated smooth muscleManual Assertion Based On ExperimentIBA:GO_Central
Response to calcium ionManual Assertion Based On ExperimentIDA:UniProtKB
Response to carbon monoxideManual Assertion Based On ExperimentIDA:UniProtKB
Response to hypoxiaManual Assertion Based On ExperimentIDA:UniProtKB
Response to osmotic stressManual Assertion Based On ExperimentIDA:UniProtKB
Smooth muscle contraction involved in micturitionManual Assertion Based On ExperimentIDA:UniProtKB

Cellular Location

Cell membrane

Involvement in disease

Paroxysmal nonkinesigenic dyskinesia, 3, with or without generalized epilepsy (PNKD3):
An autosomal dominant neurologic disorder characterized by absence seizures, generalized tonic-clonic seizures, paroxysmal nonkinesigenic dyskinesia and involuntary dystonic or choreiform movements. Onset is usually in childhood. Patients may have seizures only, dyskinesia only, or both.
Epilepsy, idiopathic generalized 16 (EIG16):
An autosomal dominant form of idiopathic generalized epilepsy, a disorder characterized by recurring generalized seizures in the absence of detectable brain lesions and/or metabolic abnormalities. Generalized seizures arise diffusely and simultaneously from both hemispheres of the brain. Seizure types include juvenile myoclonic seizures, absence seizures, and generalized tonic-clonic seizures. EIG16 is characterized by onset of seizures soon after birth or in the first years of life.
Cerebellar atrophy, developmental delay, and seizures (CADEDS):
An autosomal recessive disease characterized by epilepsy, developmental delay and severe cerebellar atrophy.
Liang-Wang syndrome (LIWAS):
An autosomal dominant syndrome characterized by a highly variable phenotype and severity. The broad spectrum of clinical features includes developmental delay, intellectual disability, ataxia, axial hypotonia, and poor or absent speech, visceral and cardiac malformations, connective tissue presentations with arterial involvement, bone dysplasia and characteristic craniofacial dysmorphism. About half of patients have cerebral and cerebellar atrophy, and thin corpus callosum.

Topology

Extracellular: 1-86
Helical: 87-107
Cytoplasmic: 108-178
Helical: 179-199
Extracellular: 200-214
Helical: 215-235
Cytoplasmic: 236-239
Helical: 240-260
Extracellular: 261-264
Helical: 265-285
Cytoplasmic: 286-300
Helical: 301-321
Extracellular: 322-335
Pore-forming: 336-358
Extracellular: 359-367
Helical: 368-388
Cytoplasmic: 389-1236

PTM

Phosphorylated (Probable). Phosphorylation by kinases such as PKA and/or PKG. In smooth muscles, phosphorylation affects its activity.
Palmitoylation by ZDHHC22 and ZDHHC23 within the intracellular linker between the S0 and S1 transmembrane domains regulates localization to the plasma membrane. Depalmitoylated by LYPLA1 and LYPLAL1, leading to retard exit from the trans-Golgi network.