Official Full Name
potassium voltage-gated channel, Shaw-related subfamily, member 1
Ion channels are integral membrane proteins that help establish and control the small voltage gradient across the plasma membrane of living cells by allowing the flow of ions down their electrochemical gradient. They are present in the membranes that surround all biological cells and their main function is to regulate the flow of ions across this membrane. Whereas some ion channels permit the passage of ions based on charge, others conduct based on a ionic species, such as sodium or potassium. Furthermore, in some ion channels, the passage is governed by a gate which is controlled by chemical
or electrical signals, temperature, or mechanical forces. There are a few main classifications of gated ion channels. There are voltage-gated ion channels, ligand- gated, other gating systems, and finally those that are classified differently, having more exotic characteristics. The first are voltagegated ion channels which open and close in response to membrane potential. These are then seperated into sodium,
calcium, potassium, proton, transient receptor, and cyclic nucleotide-gated channels, each of which is responsible for a unique role. Ligand-gated ion channels are also known as ionotropic receptors and they open in response to specific ligand
molecules binding to the extracellular domain of the receptor protein. The other gated classifications include activation and inactivation by second messengers, inward- rectifier potassium channels, calcium-activated potassium channels, two-poredomain
potassium channels, light-gated channels, mechano-sensitive ion channels, and cyclic nucleotide-gated channels. Finally, the other classifications are based on less normal characteristics such as two-pore channels and transient receptor potential channels. Potassium voltage-gated channel, Shaw-related subfamily, member 1, also known as KCNC1 or Kv3.1, is a human gene. The Shaker gene family of Drosophila encodes components of voltage-gated potassium channels and is comprised of four subfamilies. Based in sequence similarity, this gene is similar to one of these subfamilies, namely the Shaw subfamily. The protein encoded by this gene belongs to the delayed rectifier class of channel proteins and is an integral membrane protein that mediates the voltage-dependent potassium ion permeability of excitable membranes. Kv3.1b has been extensively tested in the auditory regions of mammals, and the decline of Kv3.1b expression appears to correlate with the functional decline in the medial olivocochlear efferent system. Other research shows potential for Kv3.1b channels to be oxygen
KCNC1; potassium voltage gated channel, Shaw-related subfamily, member 1; potassium voltage-gated channel subfamily C member 1; voltage-gated potassium channel subunit Kv4; voltage-gated potassium channel subunit Kv3.1; KV4; NGK2; Shaw; Kv3.1; Kcr2-1; KSh; potassium voltage-gated channel, Shaw-related subfamily, member 1; voltage-gated potassium channel protein KV3.1; FLJ41162; FLJ42249; FLJ43491; MGC129855
Voltage-gated potassium (KCN) channels are a diverse group of channels and play a central role in neuronal excitability. They contribute to the determination of the resting membrane potential, shaping of action potentials, the modulation of transmitter release and pattern of action potential discharges, and the regulation of frequency. Channels formed by Shaw-like KCNC subunits activate rapidly at potentials positive to-10 mV.
KCNC1 encodes Kv3.1, which functions as a highly conserved potassium ion channel subunit of the Kv3 subfamily of voltage-gated tetrameric potassium ion channels, major determinants of high-frequency neuronal firing. Kv3.1 is expressed in cerebellar granule cells, the thalamic reticular nucleus, a subset of cells in cerebral cortex and hippocampus, and several brainstem nuclei involved in auditory signal processing. It appears that, with the exception of cerebellar granule cells, Kv3.1 channels are expressed in parvalbumin-containing, fast-spiking GABAergic neurons. Outside the central nervous system, Kv3.1 is expressed in skeletal muscle and in T-lymphocytes.
It has been reported that a recurrent de novo mutation in KCNC1 causes progressive myoclonus epilepsy (PME). PME is one of the most destructive types of epilepsy. They are clinically and genetically heterogeneous, characterized by core features of action myoclonus, progressive neurological decline and tonic-clonic seizures. Most of the molecular characteristics of PMEs are inherited by autosomal recessive inheritance, with rare cases showing autosomal dominant or mitochondrial inheritance.
Computer simulations have suggested that the KCNC1 conductance improves postsynaptic temporal coding precisio by reducing the width of the action potential without compromising its amplitude. In the rat, alternative splicing of the KCNC1 gene gives rise to two proteins, KCNC1a and KCNC1b. Splicing varieties differ in their carboxyl termini. The in vivo expression of the two KCNC1 gene products in rat is temporally regulated during development such that KCNC1a is predominant in the embryonic and neonatal neurons, while levels of KCNC1b expression are up-regulated after postnatal day 10. In the chicken, a high threshold potassium current with kinetics similar to that of KCNC1 has been reported in developing neurons in vitro.
Poirier K, et al. Loss of Function of KCNC1 is associated with intellectual disability without seizures. European Journal of Human Genetics, 2017, 25(5).
Muona M, et al. A recurrent de novo mutation in KCNC1 causes progressive myoclonus epilepsy. Nature Genetics, 2015, 47(1):39-46.