The Role of Kv1.2 Channel in Electrotaxis Cell Migration

Abstract

Voltage‐gated potassium Kv1.2 channels play pivotal role in maintaining of resting membrane potential and, consequently, regulation of cellular excitability of neurons. Endogenously generated electric field (EF) have been proven as an important regulator for cell migration and tissue repair. The mechanisms of ion channel involvement in EF‐induced cell responses are extensively studied but largely are poorly understood. In this study we generated three COS‐7 clones with different expression levels of Kv1.2 channel, and confirmed their functional variations with patch clamp analysis. Time‐lapse imaging analysis showed that EF‐induced cell migration response was Kv1.2 channel expression level depended. Inhibition of Kv1.2 channels with charybdotoxin (ChTX) constrained the sensitivity of COS‐7 cells to EF stimulation more than their motility. Immunocytochemistry and pull‐down analyses demonstrated association of Kv1.2 channels with actin‐binding protein cortactin and its re‐localization to the cathode‐facing membrane at EF stimulation, which confirms the mechanism of EF‐induced directional migration. This study displays that Kv1.2 channels represent an important physiological link in EF‐induced cell migration. The described mechanism suggests a potential application of EF which may improve therapeutic performance in curing injuries of neuronal and/or cardiac tissue repair, post operational therapy, and various degenerative syndromes. J. Cell. Physiol. 231: 1375–1384, 2016. © 2015 The Authors. Journal of Cellular Physiology Published by Wiley Periodicals, Inc.

Identification, chemical synthesis, structure, and function of a new KV1 channel blocking peptide from Oulactis sp.

“…[74] Peptide toxins that selectively block K V 1.2 channels can be used to modulate the endogenously generated electric field in curing neuronal and cardiac tissue repair. [75,76] OspTx2a-p1 and OspTx2a- Figure 5A). Despite having a similar structure to highly potent K V 1.3blocking peptides from sea anemones such as ShK (IC 50 10 pM) [17] and BgK (IC 50 3.6 nM), [19] OspTx2a is not active against this channel.…”

“…K V 1.2 channels are predominantly present in the brain and spinal cord, regulating terminal hyperexcitability during the depolarizing after‐potential, whereas K V 1.6 channels are distributed in somatic regions mediating somatic currents in association with K V 1.1 and K V 1.2 channels . Peptide toxins that selectively block K V 1.2 channels can be used to modulate the endogenously generated electric field in curing neuronal and cardiac tissue repair . OspTx2a‐p1 and OspTx2a‐p2 are active against K V 1.2 and K V 1.6 channels in the low µM range (Figure A).…”

Long Noncoding RNA Kcna2 Antisense RNA Contributes to Ventricular Arrhythmias via Silencing Kcna2 in Rats With Congestive Heart Failure

“…Moreover, Kcna2 channels have been shown to play a pivotal role in maintaining the resting membrane potential and, consequently, regulating cellular excitability in neurons. 28 There is direct evidence showing that the I Ks is generated by Kcna2 in Xenopus oocytes, rabbit vascular myocytes, pulmonary arterial smooth muscle cells, rat mesenteric artery smooth muscle cells, and canine colonic circular smooth muscles. [29][30][31][32][33] Specifically, Kcna2 was demonstrated to contribute to the I Ks, rather than the transient outward potassium current, in adult rat myocytes.…”

Voltage-gated ion channels mediate the electrotaxis of glioblastoma cells in a hybrid PMMA/PDMS microdevice

“…VGKCs are involved in diverse physiological and pathological processess regulating the repolarization of neuromuscular action potential, calcium homeostasis, cellular proliferation, migration, and cancer proliferation [83][84][85][86][87][88][89] . Voltage-gated potassium channel K v 1.2 90 and non voltage-gated inwardly-rectifying potassium channel K ir 4.2 91 have been shown to be involved in the sensing of electric field and signaling of cell electrotaxis. The potassium ion transporters confer biophysical signals that are key for regulating stem cells and tumor cells behavior in microenvironment 92 .…”