Potassium voltage-gated channel(KCNA3)

Potassium voltage-gated channel(KCNA3) is a protein that in humans is encoded by the KCNA3 gene. It belongs to the delayed rectifier class, members of which allow nerve cells to efficiently repolarize following an action potential. It plays an essential role in T cell proliferation and activation.

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An Overview of Potassium voltage-gated channel (KCNA3)

Potassium voltage-gated channel (abbreviated as KCNA3) belongs to shaker-related subfamily of member 3. KCNA3 encodes the voltage-gated Kv1.3 channel, which is expressed in T and B lymphocytes. All human T cells express roughly 300 Kv1.3 channels per cell. From a functional and structural point of view, KCNA3 is the most complex voltage-gated ion channel. As a central channel with a divergent filter property consisting of a homotetramer and four transmembrane protein subunits, KCNA3 channel can conduct ions, which can make the potassium ions pass smoothly. There will be one or two P-loop regions on each transmembrane protein subunit. P-loop is a highly guarded P loopback region (Fig. 1). KCNA3 has multiple functions such as regulation of neurotransmitter release, heart rate, insulin secretion, neuronal excitability, epithelial electrolyte transport, smooth muscle contraction and cell volume.

Major types of KCNA3

There are a large number of potassium voltage-gated channel families, which can be divided into 10 families, named KCNA, KCNAB, KCNB, KCNC, KCND, KCNF, KCNG, KCNH, KCNQ, KCNS and KCNV according to human gene names. Corresponding to channel names, they are divided into Kv1, Kvβ, Kv2 (Kv8), Kv3, Kv4, Kv5, Kv6, Kv10 (Kv11, Kv12), Kv7, Kv9. Although the potassium voltage-gated channels have different names, they all represent the same type of channel.

Inhibition of KCNA3

At present, there are many KCNA3 inhibitors has been developed. Among them, 4-Aminopyridine (4-AP) is a potent, non-selective voltage gated potassium channels (Kv) inhibitor with IC50s of 170 μM and 230 μM for Kv1.1 and Kv1.2 in CHO cells, respectively. Repaglinide is a potassium channel blocker that lowers blood sugar by stimulating the release of the total pancreatic insulin and is used to treat type II diabetes. Nicorandil is a potassium channel activator and activates ornithine cyclase to increase the formation of cyclic ornithine. Retigabine is a novel anti-caries agent that is active in a wide range of convulsion models. Retigabine exerts its activity primarily as a KCNQ2-5 voltage-gated potassium channel in open neurons.

MCH1 and diseases

KCNA3 mutations have been described in episodic neurological disease, kidney disease, heart disease, mental disorder. KCNA3 is a new target for the treatment of neuroimmune disease multiple sclerosis.


Michael, F. W., Natali, A. M., Giovanni, S., Karla, P. F., John, P. A. B., Dagmar, N., Allan, F. M., Virgilio, G. H. E., Dominic, B. F., Ulrich, M., Alexandra, D., Alexis, B., Diane, M. P., Stefan, M. P. (2018) Mutations in voltage-gated potassium channel KCNC3 cause degenerative and developmental central nervous system phenotypes. Nature Gene. 38 (4): 447-451.