KCNC4 Membrane Protein Introduction

Introduction of KCNC4

KCNC4, also known as Kv3.4, is an integral membrane protein that belongs to the Kv3 subfamily of voltage-gated potassium channels. The Kv3 subfamily is composed of the subunits Kv3.1-3.4 that can be constructed as either homotetrameric potassium channels or heterotetrameric potassium channels. KCNC4 protein encoded by KCNC4 gene has 635 amino acid residues and contains 6 transmembrane segments (S1-S6) with a voltage-sensor in S4. It is primarily expressed in the brain and kidney.

Function of KCNC4 Membrane Protein

KCNC4 is a voltage-gated potassium channel that regulates the transportation of potassium ions across the membrane in accordance with their electrochemical gradient. The channel can alter its opened or closed conformations in response to the voltage difference across the membrane, thereby controlling potassium ion permeability of excitable membranes. In heterologous expression systems, KCNC1 and KCNC2 subunits regulate slow-inactivation delayed rectifier-type currents, whereas KCNC4 protein involves in the production of fast-inactivating A-type currents. In skeletal muscle, the KCNC4-containing voltage-gated potassium channels regulate the resting potential of muscle cells. In addition, the abnormal expression of KCNC4 has been involved in the pathological process of many types of cancer. The early occurrence and high prevalence of abnormal KCNC4 expression are observed in oral leucoplakias, which supports the role of KCNC4 in oral squamous cell carcinomas tumorigenesis. And KCNC4 plays an important role in the development and progression of head and neck squamous cell carcinomas, which suggests KCNC4 can be regarded as a biomarker for cancer risk assessment. Besides, KCNC4 is also associated with the pathological process of Alzheimer disease. The KCNC4 overexpression is observed in early stages of Alzheimer disease and in advanced stages.

Fig.1 Proposed mechanism and some questions remaining in the roles of MiRP2 and Kv3.4 subunits in apoptosis in AD. (Choi, 2007)

Application of KCNC4 Membrane Protein in Literature

1. Fernándezvalle Á., et al. Expression of the voltage-gated potassium channel Kv3.4 in oral leukoplakias and oral squamous cell carcinomas. Histopathology. 2015, 69(1):91-98. PubMed ID: 26648458
   
   

   The study suggests that Kv3.4 potassium channel exerts an important role in oral squamous cell carcinomas tumorigenesis rather than the progression of tumor and outcome of diseases.

2. Ritter D.M., et al. Dysregulation of Kv3.4 channels in dorsal root ganglia following spinal cord injury. Journal of Neuroscience the Official Journal of the Society for Neuroscience. 2015, 35(3):1260-73. PubMed ID: 25609640
   
   

   The study highlights a novel peripheral mechanism of post-SCI (spinal cord injury) pain sensitization implicating Kv3.4 channel dysregulation and potential Kv3.4-based therapeutic interventions.

3. Palme D., et al. Kv3.4 potassium channel-mediated electrosignaling controls cell cycle and survival of irradiated leukemia cells. Pflugers Arch. 2013, 465(8):1209-21. PubMed ID: 23443853
   
   

   The study indicates that electrosignaling mediated by Kv3.4 potassium channel may be involved in the regulation of cell cycle and survival of irradiated leukemia cells.

4. Menéndez S.T., et al. Expression and clinical significance of the Kv3.4 potassium channel subunit in the development and progression of head and neck squamous cell carcinomas. Journal of Pathology. 2010, 221(4):402-10. PubMed ID: 20593490
   
   

   The research shows that Kv3.4 plays an important role in malignant transformation, which suggests Kv3.4 expression may act as a biomarker for cancer risk assessment.

5. Miguelvelado E., et al. Cell cycle-dependent expression of Kv3.4 channels modulates proliferation of human uterine artery smooth muscle cells. Cardiovascular Research. 2010, 86(3):383-391. PubMed ID: 20093253
   
   

   The study shows that Kv3.4 channels play a permissive role in the uterine vascular smooth muscle cells (VSMCs) cycle progression and Kv3.4 blockade can induce cell cycle arrest after G2/M phase completion.

KCNC4 Preparation Options

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Reference

1. Choi E and Abbott G W. (2007). The MiRP2-Kv3.4 potassium channel: muscling in on Alzheimer's disease. Molecular Pharmacology. 72(3): 499-501.

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