KCNA5 Membrane Protein Introduction

Introduction of KCNA5

KCNA5, encoded by KCNA5 gene, is a member of potassium channel, voltage-gated, shaker-related subfamily which regulates the transportation of potassium ions across the membrane in accordance with their electrochemical gradient. The functional potassium channels are homotetrameric or heterotetrameric. And heterotetrameric channels contain four members such as KCNA1, KCNA2, KCNA4, KCNA5, and other KCNA members. KCNA5 protein has 613 amino acids and contains 6 transmembrane segments (S1-S6) with a shaker-type repeat in S4. It is widely present throughout the body including the skeletal and smooth muscle, kidneys, and brain.

Function of KCNA5 Membrane Protein

KCNA5 functions as a voltage-gated potassium channel involved in the regulation of potassium ion permeability of excitable membranes. It belongs to the delayed rectifier class and regulates the recovery of resting membrane potential after depolarization. KCNA5 has been revealed to participate in the regulation of many biological processes. In the central nervous system, KCNA5 regulates the ultrarapid potassium current and involves the proliferation of microglial cells and the production and release of nitric oxide. In the heart, KCNA5 is associated with the regulation of atrial mechanical dynamics via the mediation of action potential duration of atrial myocytes. And the gain-of-function mutations or loss-of-function mutations in KCNA5 have different functional effects on atrial mechanical contraction. The gain-of-function mutations reduce the action potential duration of atrial myocytes, stabilize and enhance re-entrant excitation in atrial tissue. While the loss-of-function mutations have heterogeneous effects on action potential duration and facilitate early-after-depolarisations following beta-adrenergic stimulation. KCNA5 nonsense mutations have been shown to extend the action potential duration and involve the development of familial atrial fibrillation, even sudden cardiac death. Furthermore, KCNA5 also plays a role in pulmonary vascular function through regulating the resting membrane potential and involves pulmonary vasoconstriction during hypoxic state. In addition, KCNA5 has been reported to exert a role in the progression of tumors such as Ewing sarcoma, osteosarcoma.

Fig.1 Overview of the epigenetic repression of KCNA5 in Ewing sarcoma cancer cells. (Ryland, 2016)

Application of KCNA5 Membrane Protein in Literature

1. Zhang F., et al. Association between connexin 40 and potassium voltage-gated channel subfamily A member 5 expression in the atrial myocytes of patients with atrial fibrillation. Exp Ther Med. 2017, 14(5):5170-5176. PubMed ID: 29201233
   
   

   The study shows that the decreased expression of Cx40 and KCNA5 is observed in the atrial myocytes of patients with atrial fibrillation (AF). And the Cx40 mRNA levels are positively associated with the KCNA5 mRNA.

2. Ni H., et al. In-silico investigations of the functional impact of KCNA5 mutations on atrial mechanical dynamics. J Mol Cell Cardiol. 2017, 111:86-95. PubMed ID: 28803858
   
   

   The study shows that the gain-of-function mutations or loss-of-function mutations in KCNA5 have different functional effects on atrial mechanical contraction via either decreasing or enhancing atrial output.

3. Colman M.A., et al. In silico assessment of genetic variation in KCNA5 reveals multiple mechanisms of human atrial arrhythmogenesis. PLoS Comput Biol. 2017, 13(6):e1005587. PubMed ID: 28622331
   
   

   The study indicates that the gain-of-function mutations in KCNA5 reduce the action potential duration in single cells, and stabilize and enhance re-entrant excitation in atrial tissue. While the loss-of-function mutations in KCNA5 have heterogeneous effects on action potential duration and facilitate early-after-depolarisations following beta-adrenergic stimulation.

4. Yang B., et al. Inhibition of potassium currents is involved in antiarrhythmic effect of moderate ethanol on atrial fibrillation. Toxicol Appl Pharmacol. 2017, 322:89-96. PubMed ID : 28284858
   
   

   The study indicates that ethanol intake extends the action potential duration of atrial myocytes by suppression of ultra-rapid delayed rectified potassium currents (IKv1.5) and rapid delayed rectifier potassium currents (IhERG), which is responsible for the development of atrial fibrillation.

5. Goodwill A.G., et al. Critical contribution of KV1 channels to the regulation of coronary blood flow. Basic Research in Cardiology. 2016, 111(5):56. PubMed ID: 27496159
   
   

   The study supports that KV1 play a very important role in regulating baseline coronary vascular tone, and vasodilation in response to increased transient ischemia and metabolism.

KCNA5 Preparation Options

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Reference

1. Ryland K E, et al. (2016). Ion channel silencing supports Ewing sarcoma cell proliferation. Mol Cancer Res. 14(1): 26-34.

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