KCND1 Membrane Protein Introduction

Introduction of KCND1

KCND1, also known as Kv4.1, is an integral membrane protein that belongs to the Kv4 subfamily of voltage-gated potassium channels. There are four members in Kv4 subfamily including Kv4.1, Kv4.2, and two Kv4.3 splice variants. KCND1 protein encoded by KCND1 gene has 647 amino acid residues. It possesses six putative transmembrane segments (S1-S6) with a voltage-sensor in S4, flanked by intracellular domains of variable length and a pore domain P between S5 and S6. KCND1 is highly expressed in brain, in particular in cerebellum and thalamus.

Function of KCND1 Membrane Protein

KCND1 is a voltage-gated potassium channel that plays an important role in the regulation of potassium ion permeability of excitable membranes in accordance with their electrochemical gradient. It functions in the repolarization of membrane action potentials. KCND1 generates fast-inactivating or A-type K⁺ currents (IA) including the fast-transient outward current I(To) that regulates the initial repolarization of the action potential in cardiac ventricular myocytes. Mutations in the KCND genes are associated with diseases related to altered cardiac and/or neuronal excitability. And KCND1 has been regarded as a therapeutic target for arrhythmia. Moreover, the activity of voltage-gated potassium channels plays an important role in a number of physiological processes including mediation of neurotransmitter release, insulin secretion, heart rate, and smooth muscle contraction. In addition, KCND1 is also involved in the progression of tumors. And KCND1 has been revealed a role in the proliferation of human gastric cancer cells and tumorigenic human mammary epithelial cells.

Fig.1 Structure of voltage-gated potassium channels. (Blunck, 2012)

Application of KCND1 Membrane Protein in Literature

1. Hermanstyne T.O., et al. Acute knockdown of Kv4.1 regulates repetitive firing rates and clock gene expression in the suprachiasmatic nucleus and daily rhythms in locomotor behavior. Eneuro. 2017, 4(3). PubMed ID : 28560311
   
   

   The study suggests that acute knockdown of Kv4.1 significantly decrease the circadian period of spontaneous electrical activity, clock gene expression, and locomotor activity.

2. Li X., et al. Overexpression of tau downregulated the mRNA levels of Kv channels and improved proliferation in N2A cells. Plos One. 2015, 10(1):e0116628. PubMed ID: 25590133
   
   

   The study shows that the overexpression of microtubule binding protein tau downregulates Kv channels and reduces currents. This can explain the low sensitivity to anti-cancer chemicals in some specific cancer tissues.

3. Kim H., et al. Involvement of Kv4.1 K⁺ channels in gastric cancer cell proliferation. Biological & Pharmaceutical Bulletin. 2010, 33(10):1754-7. PubMed ID: 20930388
   
   

   The study shows a role of Kv4.1 K⁺ Channels in the proliferation of the human gastric cancer cells and Kv4.1 can be regarded as a target for the treatment of gastric cancer.

4. Jang S.H., et al. Silencing of Kv4.1 potassium channels inhibits cell proliferation of tumorigenic human mammary epithelial cells. Biochemical & Biophysical Research Communications. 2009, 384(2):180-186. PubMed ID: 19401188
   
   

   The study indicates the function of Kv4.1 in the proliferation of tumorigenic human mammary epithelial cells. The increased expression of Kv4.1 may be a useful diagnostic marker for staging mammary tumors. And Kv4.1 blockage can inhibit the proliferation of tumor cell.

5. Sukigara S., et al. Expression of astrocyte-related receptors in cortical dysplasia with intractable epilepsy. Journal of Neuropathology & Experimental Neurology. 2014, 73(8):798-806. PubMed ID: 25003238
   
   

   The immunoblotting data show a higher level of Kv4.1 receptor expression in patients with cortical dysplasia with intractable epilepsy.

KCND1 Preparation Options

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Reference

1. Blunck R and Batulan Z. (2012). Mechanism of electromechanical coupling in voltage-gated potassium channels. Frontiers in Pharmacology. 3: 166.

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