KCNA4 Membrane Protein Introduction

Introduction of KCNA4

KCNA4, encoded by KCNA4 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. KCNA4 protein has 653 amino acids and contains 6 transmembrane segments (S1-S6) with a shaker-type repeat in S4 and the pore region between S5-S6. KCNA4 is the only Kv1 subunit that contains an N terminal tandem inactivation domain which regulates the fast inactivation of the channel.

Function of KCNA4 Membrane Protein

KCNA4 functions as a potassium channel involved in the regulation of voltage-dependent potassium ion permeability of excitable membranes. It has been revealed that homotetrameric of KCNA4 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 KCNA1 and KCNA4 displays rapid inactivation. Functional studies indicated that KCNA4 may be involved in the fast repolarizing phase of action potentials in heart and thus influence the duration of the cardiac action potential. Besides, KCNA4 is also involved in the regulation of neuropathic pain by controlling the hyperexcitability of primary sensory neurons. KCNA4 has been detected in nociceptive sensory neurons. And the lower expression of KCNA4 is observed in a Chung model of neuropathic pain. Furthermore, KCNA4 is associated with the pathological process of many diseases including nervous disorders such as epilepsy, depression, autoimmune encephalomyelitis. A recent study also indicated that serum DNA methylation of KCNA4 gene is also involved in the progression of gastric cancer, which provides a new potential biomarker for gastric cancer diagnosis. In addition, KCNA4 can be regarded as promising therapeutic targets for many diseases such as epilepsy and depression.

Fig.1 Solution structure of the tandem inactivation domain (residues 1-75) of potassium channel rck4 (kv1.4).

Application of KCNA4 Membrane Protein in Literature

1. Kaya N., et al. KCNA4 deficiency leads to a syndrome of abnormal striatum, congenital cataract and intellectual disability. Journal of Medical Genetics. 2016, 53(11):786-792. PubMed ID: 27582084
   
   

   The study indicates that KCNA4 deficiency may lead to a novel autosomal recessive syndrome manifesting congenital cataract, striatal thinning and attention deficit hyperactivity disorder.

2. Yeom H.D and Lee J.H. Regulation of human Kv1.4 channel activity by the antidepressant metergoline. Biological & Pharmaceutical Bulletin. 2016, 39(6):1069-1072. PubMed ID: 27251511
   
   

   The study shows that antidepressant metergoline may regulate the activity of Kv1.4 channel, which may be one of the pharmacological mechanisms of metergoline-mediated psychoactivity.

3. Chu H., et al. Integrated network analysis reveals potentially novel molecular mechanisms and therapeutic targets of refractory epilepsies. Plos One. 2017, 12(4):e0174964. PubMed ID: 28388656
   
   

   The study identifies ten potential drug targets including KCNA1, KCNA4-6, KCNC3, KCND2, KCNMA1, CAMK2G, CACNB4 and GRM1 for refractory epilepsies.

4. Sato T., et al. Type 2 diabetes induces subendocardium-predominant reduction in transient outward K⁺ current with downregulation of Kv4.2 and KChIP2. American Journal of Physiology Heart & Circulatory Physiology. 2014, 306(7):1054-65. PubMed ID: 24486512
   
   

   The study shows that type 2 diabetes mellitus (T2DM) leads to the subendocardium-predominant reduction in transient outward potassium ion current via downregulating the expression of Kv4.2 and KChIP2.

5. Carrasquillo Y., et al. A-type K⁺ channels encoded by Kv4.2, Kv4.3 and Kv1.4 differentially regulate intrinsic excitability of cortical pyramidal neurons. Journal of Physiology. 2012, 590(16):3877-3890. PubMed ID: 22615428
   
   

   The study shows that Kv4.2, Kv4.3, and Kv1.4 are both involved in the regulation of intrinsic excitability of mature cortical pyramidal neurons however the functions of them are different. Compared to Kv4.2 and Kv4.3, the loss of Kv1.4 has a minimal effect on the intrinsic excitability of mature cortical pyramidal neurons.

KCNA4 Preparation Options

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