KCNA2 Membrane Protein Introduction

Introduction of KCNA2

KCNA2, encoded by KCNA2 gene, is a member of potassium channel, voltage-gated, shaker-related subfamily which regulates the transportation of potassium ions across membrane in accordance with their electrochemical gradient. The channel consists of four subunits which interact with Kvβ subunit tetramer. Each subunit has 499 amino acids and contains 6 transmembrane segments (S1-S6) with a shaker-type repeat in S4 forming the voltage-sensor, and with the pore region between S5-S6 containing a selectivity filter and gating ion flow.

Function of KCNA2 Membrane Protein

KCNA2 is widely expressed in the brain and the central nervous system where it participates in the regulation of neuronal action potentials, neuronal excitability, and neurotransmitter release. It has been revealed that homotetrameric KCNA2 functions as a delayed rectifier potassium channel which opens in response to membrane depolarization, subsequently via slow spontaneous channel closure. And the heteromultimer assembled by KCNA2 and KCNA4 displays rapid inactivation. The KCNA2 deficiency may lead to hyperexcitability and unnormal action potential. And the loss-of-function mutations in KCNA2 have been suggested to be associated with neuronal disorders such as ataxia, pharmacoresponsive epilepsy, and hereditary spastic paraplegia. Furthermore, the association between KCNA2 mutations and the clinical phenotype of epileptic encephalopathy is well known. KCNA2 mutations (1214 C > T, 889C > T, and 1195 G > A) have been identified to be associated with novel characteristics of epileptic encephalopathy including continuous polymyoclonus, electrical status epilepticus of sleep and status epilepticus. In addition, KCNA2 is also involved in the pathological process of congestive heart failure (CHF). The deficiency of Kcna2 lead to the reduced potassium current, action potentials prolongation, and the occurrence of ventricular arrhythmias.

Fig.1 Structure of the KCNA2 protein.

Application of KCNA2 Membrane Protein in Literature

1. Niday Z and Tzingounis A.V. Potassium channel gain of function in epilepsy: an unresolved paradox. Neuroscientist. 2018, 24(4):368-380. PubMed ID: 29542386
   
   

   The review summarizes the development of the field with regard to the gain-of-function potassium channel variants associated with epilepsy (KCNA2, KCNB1, KCND2, KCNH1, KCNH5, KCNJ10, KCNMA1, KCNQ2, KCNQ3, and KCNT1). This may provide new therapeutic strategies for epilepsy.

2. Long Q.Q., et al. Long Noncoding RNA Kcna2 antisense RNA contributes to ventricular arrhythmias via silencing Kcna2 in rats with congestive heart failure. Journal of the American Heart Association, 2017, 6(12):e005965. PubMed ID: 29263036
   
   

   The study shows that the ventricular Kcna2 is upregulated in rats with congestive heart failure (CHF) and the deficiency of Kcna2 leads to the reduced potassium current, action potentials prolongation, and the occurrence of ventricular arrhythmias. This suggests that Kcna2 is a new therapeutic target for ventricular arrhythmias in patients with CHF.

3. Miao X.R., et al. DNMT3a contributes to the development and maintenance of bone cancer pain by silencing Kv1.2 expression in spinal cord dorsal horn. Molecular Pain. 2017, 13:1744806917740681. PubMed ID: 29056068
   
   

   The study shows that increased DNMT3a in dorsal horn leads to bone cancer pain through inhibiting dorsal horn Kv1.2 expression.

4. Masnada S., et al. Clinical spectrum and genotype-phenotype associations of KCNA2-related encephalopathies. Brain. 2017, 140(9):2337-2354. PubMed ID: 29050392
   
   

   The study shows the strong genotype-phenotype associations between three subgroups of patients with KCNA2 encephalopathy according to the electrophysiological features of the mutations.

5. Sachdev M., et al. Novel clinical manifestations in patients with KCNA2 mutations. Seizure. 2017, 51:74-76. PubMed ID: 28806589
   
   

   The study identifies the novel characteristics in 3 epileptic encephalopathy patients with KCNA2 mutations, including electrical status epilepticus of sleep, continuous polymyoclonus and status epilepticus.

KCNA2 Preparation Options

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