Kv4 Assays

Background of Kv4

A vast number of subfamilies have been found in the voltage-gated K⁺ channels (Kv channels) family, among which Kv4 mediates fast A-type K⁺ currents, with or without an auxiliary unit. Kv4, also known as the Shal-type family, can be activated at subthreshold membrane potential, followed by rapid inactivation and recovery, resulting in a transient current.

Fig.1. Structure Prediction of the Human Kv4. (Uniprot ID Q6PIL6; obtained from Alphafold)

Distributions and Functions of Kv4

Kv4 is widely distributed in most tissues in mammals, especially in the brain, smooth muscle, and heart, and is expressed in small or moderate amounts in other organs or tissues. The main function of Kv4 channels in organisms is to participate in the formation of transient outward A-type K⁺ currents in the somatodendritic regions of neurons and calcium-independent A-type K⁺ currents in cardiomyocytes through direct phosphorylation of subunits.

Sub Units and Mechanisms of Kv4

The Shal-type family is subdivided into three genes based on the difference in the amino and carboxyl termini of the encoded proteins, and these proteins are highly homologous in the transmembrane region.

Units	Gene	Mechanism	Activator	Blocker
Kv4.1	KCND1	Depolarization of the membrane results in the movement of positively charged residue fourth transmembrane α-helix, also S4 domains through the gating canal, and this movement of positive charge through the membrane electric field mediates the generation of voltage-gated currents. Although Kv4 channels have the characteristics of some common inactivation mechanisms of voltage-gated ion channels, molecular behaviors independent of these mechanisms have also been observed, which suggests that Kv4 channels may have some unique closed-state inactivation mechanism.		4-Aminopyridine KN-93 KN-93 Tetraethylammonium chloride
Kv4.2	KCND2			4-Aminopyridine KN-93 KN-93 Tetraethylammonium chloride
Kv4.3	KCND3		NS 3623 NS 5806	4-Aminopyridine KN-93 KN-93 Tetraethylammonium chloride

Assay List of Kv4 Channel

Creative Biolabs can provide a range of assays of Kv4 channels. You can choose the assay in the list or contact us for more information:

Kv4 Channels

Assay No.	Assay Name	Host Cell	Assay Type	Datasheet
S01YF-0722-KX225	Magic™ Human KCND2/KCNIP2 In Vitro Electrophysiology Assay, HEK293	HEK293	Electrophysiology Assay
S01YF-0722-KX226	Magic™ Human KCND3 In Vitro Electrophysiology Assay, HEK293	HEK293	Electrophysiology Assay

Published Data

Paper Title	IL- 6 signaling pathway contributes to exercise pressor reflex in rats with femoral artery occlusion in association with Kv4 activity in muscle afferent nerves
Journal	Physiological Reports
Published	2021
Abstract	During exercise, the sympathetic nervous system increases arterial blood pressure, myocardial/peripheral vasoconstriction, and heart rate through central commands and the motor pressor reflex. The exercise pressor reflex is amplified in patients with peripheral arterial disease and causes a marked increase in blood pressure. Circulating and in vivo levels of many pro-inflammatory cytokines and related signaling molecules, especially interleukin-6 (IL-6), can be detected during the chronic disease process caused by PAD. Previous experiments have demonstrated that the Kv4 channel, a member of the voltage-gated potassium channel subfamily, regulates the excitability of sensory neurons, transduces neuronal signals, and plays a key role in the sensitization of primary afferents and nociception. Data also shows that IL-6 can regulate the expression of Kv4 and related neuronal activity. According to the many correlations between IL-6 and Kv4, this study focuses on the relationship between IL-6 and Kv4 channels in muscle dorsal root ganglion (DRG) neurons, especially the exercise pressor reflex mediated by muscle afferents in PAD.
Result	In this study, a three-day femoral artery occlusion rat model was established, which resulted in increased oxidative stress products and activation of inflammatory signaling pathways in rat hindlimb muscles. They focus on the determination of the levels and activities of IL-6, IL-6R, and Kv4 in the DRG of PAD rats. Data shows that the expression of IL-6 and its receptors in the DRG of PAD rats was significantly increased, and IL-6 pathway inhibitors would reduce the blood pressure response of static muscle contraction. Both femoral artery ligation and IL-6/IL-6Rα fusion protein reduced the amplitude of Kv4 currents in DRG neurons, which was reversed by IL-6 trans-signaling inhibitors. Results show that IL-6 and its receptors cause excessive exercise pressor reflex in rats with femoral artery ligation, and this response involves the role of IL-6/IL-6Rα fusion protein, Kv4, and IL-6 trans-signaling pathway. Collectively, hindlimb muscle ischemia upregulates IL-6 in muscle afferents via a trans-signaling pathway, inhibiting the activity of Kv4 channels, which may lead to the modulation of the exercise pressor reflex in PAD. Fig.2. Changes of IL-6 and its receptors in femoral artery ligated mice. (Li, 2021) (Li, 2021)

Reference

Li, Q.; et al. IL-6 signaling pathway contributes to exercise pressor reflex in rats with femoral artery occlusion in association with Kv4 activity in muscle afferent nerves. Physiological Reports. 2021, 9: e14935.

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