Voltage-Gated Potassium Channels As Regulators of Cell Death

Overview

Journal Front Cell Dev Biol

Specialty Cell Biology

Date 2020 Dec 31

PMID 33381507

Citations 26

Authors

Magdalena Bachmann

Weiwei Li

Michael J Edwards

Syed A Ahmad

Sameer Patel

Ildiko Szabo

Erich Gulbins

Affiliations

Soon will be listed here.

Abstract

Ion channels allow the flux of specific ions across biological membranes, thereby determining ion homeostasis within the cells. Voltage-gated potassium-selective ion channels crucially contribute to the setting of the plasma membrane potential, to volume regulation and to the physiologically relevant modulation of intracellular potassium concentration. In turn, these factors affect cell cycle progression, proliferation and apoptosis. The present review summarizes our current knowledge about the involvement of various voltage-gated channels of the Kv family in the above processes and discusses the possibility of their pharmacological targeting in the context of cancer with special emphasis on Kv1.1, Kv1.3, Kv1.5, Kv2.1, Kv10.1, and Kv11.1.

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References

Wang H, Yang X, Guo Y, Shui L, Li S, Bai Y . HERG1 promotes esophageal squamous cell carcinoma growth and metastasis through TXNDC5 by activating the PI3K/AKT pathway. J Exp Clin Cancer Res. 2019; 38(1):324. PMC: 6647263. DOI: 10.1186/s13046-019-1284-y. View

Zeng W, Liu Q, Chen Z, Wu X, Zhong Y, Wu J . Silencing of hERG1 Gene Inhibits Proliferation and Invasion, and Induces Apoptosis in Human Osteosarcoma Cells by Targeting the NF-κB Pathway. J Cancer. 2016; 7(6):746-57. PMC: 4829562. DOI: 10.7150/jca.13289. View

Wulff H, Christophersen P, Colussi P, Chandy K, Yarov-Yarovoy V . Antibodies and venom peptides: new modalities for ion channels. Nat Rev Drug Discov. 2019; 18(5):339-357. PMC: 6499689. DOI: 10.1038/s41573-019-0013-8. View

Suzuki T, Takimoto K . Selective expression of HERG and Kv2 channels influences proliferation of uterine cancer cells. Int J Oncol. 2004; 25(1):153-9. View

Rao V, Perez-Neut M, Kaja S, Gentile S . Voltage-gated ion channels in cancer cell proliferation. Cancers (Basel). 2015; 7(2):849-75. PMC: 4491688. DOI: 10.3390/cancers7020813. View

Lasch M, Caballero Martinez A, Kumaraswami K, Ishikawa-Ankerhold H, Meister S, Deindl E . Contribution of the Potassium Channels K1.3 and K3.1 to Smooth Muscle Cell Proliferation in Growing Collateral Arteries. Cells. 2020; 9(4). PMC: 7226779. DOI: 10.3390/cells9040913. View

Horst C, Titze-de-Almeida R, Titze-de-Almeida S . The involvement of Eag1 potassium channels and miR-34a in rotenone-induced death of dopaminergic SH-SY5Y cells. Mol Med Rep. 2017; 15(4):1479-1488. PMC: 5364983. DOI: 10.3892/mmr.2017.6191. View

Garcia-Quiroz J, Garcia-Becerra R, Barrera D, Santos N, Avila E, Ordaz-Rosado D . Astemizole synergizes calcitriol antiproliferative activity by inhibiting CYP24A1 and upregulating VDR: a novel approach for breast cancer therapy. PLoS One. 2012; 7(9):e45063. PMC: 3440370. DOI: 10.1371/journal.pone.0045063. View

Jiao S, Liu Z, Ren W, Ding Y, Zhang Y, Zhang Z . cAMP/protein kinase A signalling pathway protects against neuronal apoptosis and is associated with modulation of Kv2.1 in cerebellar granule cells. J Neurochem. 2006; 100(4):979-91. DOI: 10.1111/j.1471-4159.2006.04261.x. View

10.

Breuer E, Fukushiro-Lopes D, Dalheim A, Burnette M, Zartman J, Kaja S . Potassium channel activity controls breast cancer metastasis by affecting β-catenin signaling. Cell Death Dis. 2019; 10(3):180. PMC: 6385342. DOI: 10.1038/s41419-019-1429-0. View

11.

Pieri M, Amadoro G, Carunchio I, Ciotti M, Quaresima S, Florenzano F . SP protects cerebellar granule cells against beta-amyloid-induced apoptosis by down-regulation and reduced activity of Kv4 potassium channels. Neuropharmacology. 2009; 58(1):268-76. DOI: 10.1016/j.neuropharm.2009.06.029. View

12.

Jimenez-Perez L, Cidad P, Alvarez-Miguel I, Santos-Hipolito A, Torres-Merino R, Alonso E . Molecular Determinants of Kv1.3 Potassium Channels-induced Proliferation. J Biol Chem. 2015; 291(7):3569-80. PMC: 4751396. DOI: 10.1074/jbc.M115.678995. View

13.

Vallejo-Gracia A, Bielanska J, Hernandez-Losa J, Castellvi J, Ruiz-Marcellan M, Cajal S . Emerging role for the voltage-dependent K+ channel Kv1.5 in B-lymphocyte physiology: expression associated with human lymphoma malignancy. J Leukoc Biol. 2013; 94(4):779-89. DOI: 10.1189/jlb.0213094. View

14.

Smith G, Newell E, Jiang X, Zhu X, Tsui F, Schlichter L . Functional up-regulation of HERG K+ channels in neoplastic hematopoietic cells. J Biol Chem. 2002; 277(21):18528-34. DOI: 10.1074/jbc.M200592200. View

15.

Gonzalez C, Baez-Nieto D, Valencia I, Oyarzun I, Rojas P, Naranjo D . K(+) channels: function-structural overview. Compr Physiol. 2013; 2(3):2087-149. DOI: 10.1002/cphy.c110047. View

16.

Pardo L, del Camino D, Sanchez A, Alves F, Bruggemann A, Beckh S . Oncogenic potential of EAG K(+) channels. EMBO J. 1999; 18(20):5540-7. PMC: 1171622. DOI: 10.1093/emboj/18.20.5540. View

17.

Cidad P, Moreno-Dominguez A, Novensa L, Roque M, Barquin L, Heras M . Characterization of ion channels involved in the proliferative response of femoral artery smooth muscle cells. Arterioscler Thromb Vasc Biol. 2010; 30(6):1203-11. DOI: 10.1161/ATVBAHA.110.205187. View

18.

Leanza L, Manago A, Zoratti M, Gulbins E, Szabo I . Pharmacological targeting of ion channels for cancer therapy: In vivo evidences. Biochim Biophys Acta. 2015; 1863(6 Pt B):1385-97. DOI: 10.1016/j.bbamcr.2015.11.032. View

19.

Yao H, Zhou K, Yan D, Li M, Wang Y . The Kv2.1 channels mediate neuronal apoptosis induced by excitotoxicity. J Neurochem. 2008; 108(4):909-19. DOI: 10.1111/j.1471-4159.2008.05834.x. View

20.

Norris C, He K, Springer M, Hartnett K, Horn J, Aizenman E . Regulation of neuronal proapoptotic potassium currents by the hepatitis C virus nonstructural protein 5A. J Neurosci. 2012; 32(26):8865-70. PMC: 3388847. DOI: 10.1523/JNEUROSCI.0937-12.2012. View