Abstract
K+ channels are a most diverse class of ion channels in the cytoplasmic membrane and are distributed widely in a variety of cells including cancer cells. Cell proliferation and apoptosis (programmed cell death or cell suicide) are two counterparts that share the responsibility for maintaining normal tissue homeostasis. Evidence has been accumulating from fundamental studies indicating that tumour cells possess various types of K+ channels, and that these K+ channels play important roles in regulating tumour cell proliferation and apoptosis, i.e. facilitating unlimited growth and promoting apoptotic death of tumour cells. The potential implications of K+ channels as a pharmacological target for cancer therapy and a biomarker for diagnosis of carcinogenesis are attracting increasing interest. This review aims to provide a comprehensive overview of current status of research on K+ channels/currents in tumour cells. Focus is placed on the roles of K+ channels/currents in regulating tumour cell proliferation and apoptosis. The possible mechanisms by which K+ channels affect tumour cell growth and death are discussed. Speculations are also made on the potential implications of regulation of tumour cell proliferation and apoptosis by K+ channels.
Similar content being viewed by others
References
Simonneau M, Distasi C, Tauc L, Poujeol C (1985) Development of ionic channels during mouse neuronal differentiation. J Physiol (Paris) 80:312–320
Vyklicky L Jr, Michl J, Vlachova V, Vyklicky L, Vyskocil F (1985) Ionic currents in neuroblastoma clone E-7 cells. Neurosci Lett 55:197–201
Lang DG, Ritchie AK (1987) Large and small conductance calcium-activated potassium channels in the GH3 anterior pituitary cell line. Pflugers Arch 410:614–622
Weiger T, Hermann A (1994) Polyamines block Ca2+-activated K+ channels in pituitary tumor cells (GH3). J Membr Biol 140:133–142
Li PC, Liang JT, Huang HT, Lin PH, Wu SN (2002) Enhanced activity of Ca2+-activated K+ channels by 1-[2-hydroxy-3-propyl-4-[(1H-tetrazol-5-yl)butoxyl]phenyl] ethanone (LY-171883) in neuroendocrine and neuroblastoma cell lines. J Cell Physiol 192:188–199
Li ZW, Ding JP, Kalyanaraman V, Lingle CJ (1999) RINm5f cells express inactivating BK channels whereas HIT cells express noninactivating BK channels. J Neurophysiol 81:611–624
Liu X, Chang Y, Reinhart PH, Sontheimer H, Chang Y (2002) Cloning and characterization of glioma BK, a novel BK channel isoform highly expressed in human glioma cells. J Neurosci 22:1840–1849
Basavappa S, Mangel AW, Boulpaep EL (2003) Calcium-dependent, swelling-activated K+ conductance in human neuroblastoma cells. Biochem Biophys Res Commun 308:759–763
Quandt FN (1988) Three kinetically distinct potassium channels in mouse neuroblastoma cells. J Physiol (Lond) 395:401–418
Moreau R, Aubin R, Lapointe JY, Lajeunesse D (1997) Pharmacological and biochemical evidence for the regulation of osteocalcin secretion by potassium channels in human osteoblast-like MG-63 cells. J Bone Miner Res 12:1984–1992
Roman R, Feranchak AP, Troetsch M, Dunkelberg JC, Kilic G, Schlenker T, Schaack J, Fitz J G (2002) Molecular characterization of volume-sensitive SKCa channels in human liver cell lines. Am J Physiol 282:G116–G122
Kraft R, Benndorf K, Patt S (2000) Large conductance Ca2+-activated K+ channels in human meningioma cells. J Membr Biol 175:25–33
Meyer R, Schonherr R, Gavrilova-Ruch O, Wohlrab W, Heinemann SH (1999) Identification of ether a go-go and calcium-activated potassium channels in human melanoma cells. J Membr Biol 171:107–115
Allen DH, Lepple-Wienhues A, Cahalan MD (1997) Ion channel phenotype of melanoma cell lines. J Membr Biol 155:27–34
Monen SH, Schmidt PH, Wondergem R (1998) Membrane potassium channels and human bladder tumor cells. I. Electrical properties. J Membr Biol 161:247–256
Diserbo M, Fatome M, Verdetti J (1996) Activation of large conductance Ca2+-activated K+ channels in N1E-115 neuroblastoma cells by platelet-activating factor. Biochem Biophys Res Commun 218:745–748
Lemos VS, Takeda K (1995) Neuropeptide Y2-type receptor-mediated activation of large-conductance Ca2+-sensitive K+ channels in a human neuroblastoma cell line. Pflugers Arch 430:534–540
Koong AC, Giaccia AJ, Hahn GM, Saad AH (1993) Activation of potassium channels by hypoxia and reoxygenation in the human lung adenocarcinoma cell line A549. J Cell Physiol 156:341–347
Bordey A, Sontheimer H (1998) Electrophysiological properties of human astrocytic tumor cells in situ: enigma of spiking glial cells. J Neurophysiol 79:2782–2793
Cukierman S (1992) Characterization of K+ currents in rat malignant lymphocytes (Nb2 cells). J Membr Biol 126:147–157
Skryma R, Van Coppenolle F, Dufy-Barbe L, Dufy B, Prevarskaya N (1999) Characterization of Ca2+-inhibited potassium channels in the LNCaP human prostate cancer cell line. Receptors Channels 6:241–253
O’Kelly I, Peers C, Kemp PJ (1998) O2-sensitive K+ channels in neuroepithelial body-derived small cell carcinoma cells of the human lung. Am J Physiol 275:L709–L716
Hoshi T, Aldrich RW (1988) Voltage-dependent K+ currents and underlying single K+ channels in pheochromocytoma cells. J Gen Physiol 91:73–106
Hoshi T, Aldrich RW (1988) Gating kinetics of four classes of voltage-dependent K+ channels in pheochromocytoma cells. J Gen Physiol 81:197–131
Conforti L, Millhorn DE (1997) Selective inhibition of a slow-inactivating voltage-dependent K+ channel in rat PC12 cells by hypoxia. J Physiol (Lond) 503:293–305
Fraser SP, Grimes JA, Diss JK, Stewart D, Dolly JO, Djamgoz MB (2003) Predominant expression of Kv1.3 voltage-gated K+ channel subunit in rat prostate cancer cell lines: electrophysiological, pharmacological and molecular characterisation. Pflugers Arch 446:559–571
Abdul M, Santo A, Hoosein N (2003) Activity of potassium channel-blockers in breast cancer. Anticancer Res 23:3347–3351
Zhou ZH, Unlap T, Li L, Ma HP (2002) Incomplete inactivation of voltage-dependent K+ channels in human B lymphoma cells. J Membr Biol 188:97–105
Preussat K, Beetz C, Schrey M, Kraft R, Wolfl S, Kalff R, Patt S (2003) Expression of voltage-gated potassium channels Kv1.3 and Kv1.5 in human gliomas. Neurosci Lett 346:33–36
Ouadid-Ahidouch H, Chaussade F, Roudbaraki M, Slomianny C, Dewailly E, Delcourt P, Prevarskaya N (2000) Kv1.1 K+ channels identification in human breast carcinoma cells: involvement in cell proliferation. Biochem Biophys Res Commun 278:272–277
Ji J, Tsuk S, Salapatek AM, Huang X, Chikvashvili D, Pasyk EA, Kang Y, Sheu L, Tsushima R, Diamant N, Trimble WS, Lotan I, Gaisano HY (2002) The 25-kDa synaptosome-associated protein (SNAP-25) binds and inhibits delayed rectifier potassium channels in secretory cells. J Biol Chem 277:20195–20204
MacDonald PE, Sewing S, Wang J, Joseph JW, Smukler SR, Sakellaropoulos G, Wang J, Saleh MC, Chan CB, Tsushima RG, Salapatek AM, Wheeler MB (2002) Inhibition of Kv2.1 voltage-dependent K+ channels in pancreatic beta-cells enhances glucose-dependent insulin secretion. J Biol Chem 277:44938–44945
Su J, Yu H, Lenka N, Hescheler J, Ullrich S (2001) The expression and regulation of depolarization-activated K+ channels in the insulin-secreting cell line INS-1. Pflugers Arch 442:49–56
Akhtar S, McIntosh P, Bryan-Sisneros A, Barratt L, Robertson B, Dolly JO (1999) A functional spliced-variant of beta 2 subunit of Kv1 channels in C6 glioma cells and reactive astrocytes from rat lesioned cerebellum. Biochemistry 38:16984–16992
Nobile M, Lagostena L (1998) A discriminant block among K+ channel types by phenytoin in neuroblastoma cells. Br J Pharmacol 124:1698–1702
Meyer R, Heinemann SH (1998) Characterization of an eag-like potassium channel in human neuroblastoma cells. J Physiol (Lond) 508:49–56
Stansfeld CE, Roper J, Ludwig J, Weseloh RM, Marsh SJ, Brown DA, Pongs O (1996) Elevation of intracellular calcium by muscarinic receptor activation induces a block of voltage-activated rat ether-a-go-go channels in a stably transfected cell line. Proc Natl Acad Sci USA 93:9910–9914
Pardo LA, Bruggemann A, Camacho J, Stuhmer W (1998) Cell cycle-related changes in the conducting properties of r-eag K+ channels. J Cell Biol 143:767–775
Pardo LA, del Camino D, Sanchez A, Alves F, Bruggemann A, Beckh S, Stuhmer W (1999) Oncogenic potential of EAG K+ channels. EMBO J 18:5540–5547
Bauer CK, Schwarz JR (2001) Physiology of EAG K+ channels. J Membr Biol 182:1–15
Sanguinetti MC, Jiang C, Curran ME, Keating MT (1995) A mechanistic link between an inherited and an acquired cardiac arrhythmia: HERG encodes the IKr potassium channel. Cell 81:299–307
Bhattacharyya ML, Sarker S, Mull KP, Debnam Q (1997) Clofilium-induced block of delayed rectifier type K+ current in atrial tumor cells (AT-1 cells). J Mol Cell Cardiol 29:301–307
Yang T, Snyders DJ, Roden DM (1997) Rapid inactivation determines the rectification and [K+]o dependence of the rapid component of the delayed rectifier K+ current in cardiac cells. Circ Res 80:782–789
Kabir SM, Bhattacharyya ML, Robinson TR (2000) Indapamide blocks the rapid component of the delayed rectifier current in atrial tumor cells (AT-1 cells). Int J Cardiol 73:27–32
Claycomb WC, Lanson NA Jr, Stallworth BS, Egeland DB, Delcarpio JB, Bahinski A, Izzo NJ Jr (1998) HL-1 cells: a cardiac muscle cell line that contracts and retains phenotypic characteristics of the adult cardiomyocyte. Proc Natl Acad Sci USA 95:2979–2984
Wang H, Zhang Y, Cao L, Han H, Wang J, Yang B, Nattel S, Wang Z (2002) HERG K+ channel: A regulator of tumor cell apoptosis and proliferation. Cancer Res 62:4843–4848
Bianchi L, Wible B, Arcangeli A, Taglialatela M, Morra F, Castaldo P, Crociani O, Rosati B, Faravelli L, Olivotto M, Wanke E (1998) Herg encodes a K+ current highly conserved in tumors of different histogenesis: a selective advantage for cancer cells? Cancer Res 58:815–822
Meves H (2000) Effect of low external calcium on the ERG current of NG108-15 cells. Biochim Biophys Acta 1509:245–254
Higashida H, Brown DA, Robbins J (2000) Both linopirdine- and WAY123,398-sensitive components of IKM,ng are modulated by cyclic ADP ribose in NG108-15 cells. Pflugers Arch 441:228–234
Nastainczyk W, Meves H, Watt DD (2002) A short-chain peptide toxin isolated from Centruroides sculpturatus scorpion venom inhibits ether-a-go-go-related gene K+ channels. Toxicon 40:1053–1058
Selyanko AA, Delmas P, Hadley JK, Tatulian L, Wood IC, Mistry M, London B, Brown DA (2002). Dominant-negative subunits reveal potassium channel families that contribute to M-like potassium currents. J Neurosci 22:RC212:1–5
Cherubini A, Taddei GL, Crociani O, Paglierani M, Buccoliero AM, Fontana L, Noci I, Borri P, Borrani E, Giachi M, Becchetti A, Rosati B, Wanke E, Olivotto M, Arcangeli A (2000) HERG potassium channels are more frequently expressed in human endometrial cancer as compared to non-cancerous endometrium. Br J Cancer 83:1722–1729
Finlayson K, Pennington AJ, Kelly JS (2001) [3H]dofetilide binding in SHSY5Y and HEK293 cells expressing a HERG-like K+ channel? Eur J Pharmacol 412:203–212
Pillozzi S, Brizzi MF, Balzi M, Crociani O, Cherubini A, Guasti L, Bartolozzi B, Becchetti A, Wanke E, Bernabei PA, Olivotto M, Pegoraro L, Arcangeli A (2002) HERG potassium channels are constitutively expressed in primary human acute myeloid leukemias and regulate cell proliferation of normal and leukemic hemopoietic progenitors. Leukemia 16:1791–1798
Smith GA, Tsui HW, Newell EW, Jiang X, Zhu XP, Tsui FW, Schlichter LC (2002) Functional up-regulation of HERG K+ channels in neoplastic hematopoietic cells. J Biol Chem 277:18528–18534
Crociani O, Guasti L, Balzi M, Becchetti A, Wanke E, Olivotto M, Wymore RS, Arcangeli A (2003) Cell cycle-dependent expression of HERG1 and HERG1B isoforms in tumor cells. J Biol Chem 278:2947–2955
Bauer CK, Wulfsen I, Schafer R, Glassmeier G, Wimmers S, Flitsch J, Ludecke DK, Schwarz JR (2003) HERG K+ currents in human prolactin-secreting adenoma cells. Pflugers Arch 445:589–600
Liu YC, Wu SN (2003) Block of erg current by linoleoylamide, a sleep-inducing agent, in pituitary GH3 cells. Eur J Pharmacol 458:37–47
Lastraioli E, Guasti L, Crociani O, Polvani S, Hofmann G, Witchel H, Bencini L, Calistri M, Messerini L, Scatizzi M, Moretti R, Wanke E, Olivotto M, Mugnai G, Arcangeli A (2004) herg1 gene and HERG1 protein are overexpressed in colorectal cancers and regulate cell invasion of tumor cells. Cancer Res 64:606–611
Becchetti A, De Fusco M, Crociani O, Cherubini A, Restano-Cassulini R, Lecchi M, Masi A, Arcangeli A, Casari G, Wanke E (2002) The functional properties of the human ether-a-go-go-like (HELK2) K+ channel. Eur J Neurosci 16:415–428
Brismar T, Collins VP (1989) Inward rectifying potassium channels in human malignant glioma cells. Brain Res 480:249–258
Lewis DL, Ikeda SR, Aryee D, Joho RH (1991) Expression of an inwardly rectifying K+ channel from rat basophilic leukemia cell mRNA in Xenopus oocytes. FEBS Lett 290:17–21
Mukai M, Takada K (1991) Ca2+-dependent suppression of inwardly rectified K+ channels in rat basophilic leukemia cells. Osaka City Med J 37:53–64
Jirsch J, Deeley RG, Cole SP, Stewart AJ, Fedida D (1993) Inwardly rectifying K+ channels and volume-regulated anion channels in multidrug-resistant small cell lung cancer cells. Cancer Res 53:4156–4160
Collins A, German MS, Jan YN, Jan LY, Zhao B (1996) A strongly inwardly rectifying K+ channel that is sensitive to ATP. J Neurosci 16:1–9
Bianchi L, Arcangeli A, Bartolini P, Mugnai G, Wanke E, Olivotto M (1995) An inward rectifier K+ current modulates in neuroblastoma cells the tyrosine phosphorylation of the pp125FAK and associated proteins: role in neuritogenesis. Biochem Biophys Res Commun 210:823–829
Pancrazio JJ, Ma W, Grant GM, Shaffer KM, Kao WY, Liu QY, Manos P, Barker JL, Stenger DA (1999) A role for inwardly rectifying K+ channels in differentiation of NG108-15 neuroblastoma x glioma cells. J Neurobiol 38:466–474
Codina C, Kraft R, Pietsch T, Prinz M, Steinhauser C, Cervos-Navarro J, Patt S (2000) Voltage- and gamma-aminobutyric acid-activated membrane currents in the human medulloblastoma cell line MHH-MED-3. Neurosci Lett 287:53–56
Sakai H, Shimizu T, Hori K, Ikari A, Asano S, Takeguchi N (2002) Molecular and pharmacological properties of inwardly rectifying K+ channels of human lung cancer cells. Eur J Pharmacol 435:125–133
Sanguinetti MC, Scott AL, Zingaro GJ, Siegl PK (1988) BRL 34915 (cromakalim) activates ATP-sensitive K+ current in cardiac muscle. Proc Natl Acad Sci USA 85:8360–8364
Plant TD, Jonas JC, Henquin JC (1991) Clonidine inhibits ATP-sensitive K+ channels in mouse pancreatic beta-cells. Br J Pharmacol 104:385–390
Dunne MJ, Bullett MJ, Li GD, Wollheim CB, Petersen OH (1989) Galanin activates nucleotide-dependent K+ channels in insulin-secreting cells via a pertussis toxin-sensitive G-protein. EMBO J 8:413–420
Eddlestone GT, Ribalet B, Ciani S (1989) Comparative study of K channel behavior in beta cell lines with different secretory responses to glucose. J Membr Biol 109:123–134
Miller TR, Taber RD, Molinari EJ, Whiteaker KL, Monteggia LM, Scott VE, Brioni JD, Sullivan JP, Gopalakrishnan M (1999) Pharmacological and molecular characterization of ATP-sensitive K+ channels in the TE671 human medulloblastoma cell line. Eur J Pharmacol 370:179–185
Christensen O, Hoffmann EK (1992) Cell swelling activates K+ and Cl− channels as well as nonselective, stretch-activated cation channels in Ehrlich ascites tumor cells. J Membr Biol 129:13–36
Niemeyer MI, Cid LP, Sepulveda FV (2001) K+ conductance activated during regulatory volume decrease. The channels in Ehrlich cells and their possible molecular counterpart. Comp Biochem Physiol A Mol Integr Physiol 130:565–575
Niemeyer MI, Cid LP, Barros LF, Sepulveda FV (2001) Modulation of the two-pore domain acid-sensitive K+ channel TASK-2 (KCNK5) by changes in cell volume. J Biol Chem 276:43166–43174
Hoffmann EK, Hougaard C (2001) Intracellular signalling involved in activation of the volume-sensitive K+ current in Ehrlich ascites tumour cells. Comp Biochem Physiol A Mol Integr Physiol 130:355–366
Selyanko AA, Robbins J, Brown DA (1995) Putative M-type potassium channels in neuroblastoma-glioma hybrid cells: inhibition by muscarine and bradykinin. Receptors Channels 3:147–159
Noda M, Obana M, Akaike N (1998) Inhibition of M-type K+ current by linopirdine, a neurotransmitter-release enhancer, in NG108-15 neuronal cells and rat cerebral neurons in culture. Brain Res 794:274–280
Kuo SS, Saad AH, Koong AC, Hahn GM, Giaccia AJ (1993) Potassium-channel activation in response to low doses of gamma-irradiation involves reactive oxygen intermediates in nonexcitatory cells. Proc Natl Acad Sci USA 90:908–912
Wang L, Xu D, Dai W, Lu L (1999) An ultraviolet-activated K+ channel mediates apoptosis of myeloblastic leukemia cells. J Biol Chem 274:3678–3685
Rouzaire-Dubois B, Dubois JM (1990) Tamoxifen blocks both proliferation and voltage-dependent K+ channels of neuroblastoma cells. Cell Signal 2:387–393
Pancrazio JJ, Tabbara IA, Kim YI (1993) Voltage-activated K+ conductance and cell proliferation in small-cell lung cancer. Anticancer Res 13:1231–1234
Rouzaire-Dubois B, Gerard V, Dubois JM (1993) Involvement of K+ channels in the quercetin-induced inhibition of neuroblastoma cell growth. Pflugers Arch 423:202–205
Fieber LA, Gonzalez DM, Wallace MR, Muir D (2003) Delayed rectifier K currents in NF1 Schwann cells. Pharmacological block inhibits proliferation. Neurobiol Dis 13:136–146
Nilius B, Wohlrab W (1992) Potassium channels and regulation of proliferation of human melanoma cells. J Physiol (Lond) 445:537–548
Rouzaire-Dubois B, Dubois JM (1991) A quantitative analysis of the role of K+ channels in mitogenesis of neuroblastoma cells. Cell Signal 3:333–339
Pancrazio JJ, Viglione MP, Kleiman RJ, Kim YI (1991) Verapamil-induced blockade of voltage-activated K+ current in small-cell lung cancer cells. J Pharmacol Exp Ther 257:184–191
Wang YF, Jia H, Walker AM, Cukierman S (1992) K-current mediation of prolactin-induced proliferation of malignant (Nb2) lymphocytes. J Cell Physiol 152:185–189
Zhou Q, Kwan HY, Chan HC, Jiang JL, Tam SC, Yao X (2003) Blockage of voltage-gated K+ channels inhibits adhesion and proliferation of hepatocarcinoma cells. Int J Mol Med 11:261–266
Yao X, Kwan HY (1999) Activity of voltage-gated K+ channels is associated with cell proliferation and Ca2+ influx in carcinoma cells of colon cancer. Life Sci 65:55–62
Skryma RN, Prevarskaya NB, Dufy-Barbe L, Odessa MF, Audin J, Dufy B (1997) Potassium conductance in the androgen-sensitive prostate cancer cell line, LNCaP: involvement in cell proliferation. Prostate 33:112–122
Fraser SP, Grimes JA, Djamgoz MB (2000) Effects of voltage-gated ion channel modulators on rat prostatic cancer cell proliferation: comparison of strongly and weakly metastatic cell lines. Prostate 44:61–76
Rybalchenko V,Prevarskaya N, Van Coppenolle F, Legrand G, Lemonnier L, Le Bourhis X, Skryma R (2001) Verapamil inhibits proliferation of LNCaP human prostate cancer cells influencing K+ channel gating. Mol Pharmacol 59:1376–1387
Van Coppenolle F, Skryma R, Ouadid-Ahidouch H, Slomianny C, Roudbaraki M, Delcourt P, Dewailly E, Humez S, Crepin A, Gourdou I, Djiane J, Bonnal JL, Mauroy B, Prevarskaya N (2004) Prolactin stimulates cell proliferation through a long form of prolactin receptor and K+ channel activation. Biochem J 377:569–578
Warmke J, Drysdale R, Ganetzky B (1991) A distinct potassium channel polypeptide encoded by the Drosophila eag locus. Science 252:1560–1562
Warmke JW, Ganetzky B (1994) A family of potassium channel genes related to eag in Drosophila and mammals. Proc Natl Acad Sci USA 91:3438–3442
Ouadid-Ahidouch H, Le Bourhis X, Roudbaraki M, Toillon RA, Delcourt P, Prevarskaya N (2001) Changes in the K+ current-density of MCF-7 cells during progression through the cell cycle: possible involvement of a h-ether-a-gogo K+ channel. Receptors Channels 7:345–356
Wang L, Feng ZP, Kondo CS, Sheldon RS, Duff HJ (1996) Developmental changes in the delayed rectifier K+ channels in mouse heart. Circ Res 79:79–85
Wang L, Duff HJ (1996) Identification and characteristics of delayed rectifier K+ current in fetal mouse ventricular myocytes. Am J Physiol 270:H2088–H2093
Arcangeli A, Rosati B, Cherubini A, Crociani O, Fontana L, Ziller C, Wanke E, Olivotto M (1997). HERG- and IRK-like inward rectifier currents are sequentially expressed during neuronal development of neural crest cells and their derivatives. Eur J Neurosci 9:2596–2604
Crociani O, Cherubini A, Piccini E, Polvani S, Costa L, Fontana L, Hofmann G, Rosati B, Wanke E, Olivotto M, Arcangeli A (2000) erg gene(s) expression during development of the nervous and muscular system of quail embryos. Mech Dev 95:239–243
Hofmann G, Bernabei PA, Crociani O, Cherubini A, Guasti L, Pillozzi S, Lastraioli E, Polvani S, Bartolozzi B, Solazzo V, Gragnani L, Defilippi P, Rosati B, Wanke E, Olivotto M, Arcangeli A (2001) HERG K+ channels activation during β1 integrin-mediated adhesion to fibronectin induces an up-regulation of αvβ3 integrin in the preosteoclastic leukemia cell line FLG 29.1. J Biol Chem 276:4923–4931
Lepple-Wienhues A, Berweck S, Bohmig M, Leo CP, Meyling B, Garbe C, Wiederholt M (1996) K+ channels and the intracellular calcium signal in human melanoma cell proliferation. J Membr Biol 151:146–157
Malhi H, Irani AN, Rajvanshi P, Suadicani SO, Spray DC, McDonald TV, Gupta S (2000) KATP channels regulate mitogenically induced proliferation in primary rat hepatocytes and human liver cell lines. Implications for liver growth control and potential therapeutic targeting. J Biol Chem 275:26050–26057
Lee YS, Sayeed MM, Wurster RD (1994) In vitro antitumor activity of cromakalim in human brain tumor cells. Pharmacology 49:69–74
Huang MH, Wu SN, Chen CP, Shen AY (2002) Inhibition of Ca2+-activated and voltage-dependent K+ currents by 2-mercaptophenyl-1,4-naphthoquinone in pituitary GH3 cells: contribution to its antiproliferative effect. Life Sci 70:1185–1203
Redmann K, Muller V, Tanneberger S, Kalkoff W (1972) The membrane potential of primary ovarian tumor cells in vitro and its dependence on the cell cycle. Acta Biol Med Ger 28:853–856
Smith TC, Levinson C (1975) Direct measurement of the membrane potential of Ehrlich ascites tumor cells: lack of effect of valinomycin and ouabain. J Membr Biol 23:349–365
Lymangrover J, Pearlmutter AF, Franco-Saenz R, Saffran M (1975) Transmembrane potentials and steroidogenesis in normal and neoplastic human adrenocortical tissue. J Clin Endocrinol Metab 41:697–706
Binggeli R, Cameron IL (1980) Cellular potentials of normal and cancerous fibroblasts and hepatocytes. Cancer Res 40:1830–1835
Stevenson D, Binggeli R, Weinstein RC, Keck JG, Lai MC, Tong MJ (1989) Relationship between cell membrane potential and natural killer cell cytolysis in human hepatocellular carcinoma cells. Cancer Res 49:4842–4845
Marino AA, Morris DM, Schwalke MA, Iliev IG, Rogers S (1994) Electrical potential measurements in human breast cancer and benign lesions Tumour Biol 15:147–152
Wonderlin WF, Woodfork KA, Strobl JS (1995) Changes in membrane potential during the progression of MCF-7 human mammary tumor cells through the cell cycle. J Cell Physiol 165:177–185
Zhang J, Davidson RM, Wei MD, Loew LM (1998) Membrane electric properties by combined patch clamp and fluorescence ratio imaging in single neurons. Biophys J 74:48–53
Pandiella A, Magni M, Lovisolo D, Meldolesi J (1989) The effect of epidermal growth factor on membrane potential. Rapid hyperpolarization followed by persistent fluctuations. J Biol Chem 264:12914–12921
Lang F, Friedrich F, Kahn E, Woll E, Hammerer M, Waldegger S, Maly K, Grunicke H (1991) Bradykinin-induced oscillations of cell membrane potential in cells expressing the Ha-ras oncogene. J Biol Chem 266:4938–4942
Lang F, Waldegger S, Woell E, Ritter M, Maly K, Grunicke H (1992) Effects of inhibitors and ion substitutions on oscillations of cell membrane potential in cells expressing the RAS oncogene. Pflugers Arch 421:416–424
Lee YS, Sayeed MM, Wurster RD (1994) Inhibition of cell growth and intracellular Ca2+ mobilization in human brain tumor cells by Ca2+ channel antagonists. Mol Chem Neuropathol 22:81–95
Kim JA, Chung YJ, Lee YS (1998) Intracellular Ca2+ mediates lipoxygenase-induced proliferation of U-373 MG human astrocytoma cells. Arch Pharm Res 21:664–670
Brocchieri A, Saporiti A, Moroni M, Porta C, Tua A, Grignani G (1996) Verapamil inhibits to different extents agonist-induced Ca2+ transients in human tumor cells and in vitro tumor cell growth. Invasion Metastasis 16:56–64
Rouzaire-Dubois B, Dubois JM (1998) K+ channel block-induced mammalian neuroblastoma cell swelling: a possible mechanism to influence proliferation. J Physiol (Lond) 510:93–102
Tamatani T (2001) Enhanced IκB kinase activity is responsible for the augmented activity of NF-κB in human head and neck carcinoma cells. Cancer Lett 171:165–172
Wang L, Xu B, White RE, Lu L (1997) Growth factor-mediated K+ channel activity associated with human myeloblastic ML-1 cell proliferation. Am J Physiol 273:C1657–C1665
Xu D, Wang L, Dai W, Lu L (1999) A requirement for K+-channel activity in growth factor-mediated extracellular signal-regulated kinase activation in human myeloblastic leukemia ML-1 cells. Blood 94:139–145
De Miguel MP, Royuela M, Bethencourt FR, Santamaria L, Fraile B, Paniagua R (2000) Immunoexpression of tumour necrosis factor-α and its receptors 1 and 2 correlates with proliferation/apoptosis equilibrium in normal, hyperplastic and carcinomatous human prostate. Cytokine 12:535–538
Lindholm PF, Bub J, Kaul S, Shidham VB, Kajdacsy-Balla A (2000) The role of constitutive NF-κB activity in PC-3 human prostate cancer cell invasive behavior. Clin Exp Metastasis 18:471–479
Lang F, Ritter M, Gamper N, Huber S, Fillon S, Tanneur V, Lepple-Wienhues A, Szabo I, Gulbins E (2000) Cell volume in the regulation of cell proliferation and apoptotic cell death. Cell Physiol Biochem 10:417–428
Yu SP (2003) Regulation and critical role of potassium homeostasis in apoptosis. Prog Neurobiol 70:363–386
Lang F, Lang KS, Wieder T, Myssina S, Birka C, Lang PA, Kaiser S, Kempe D, Duranton C, Huber SM (2003) Cation channels, cell volume and the death of an erythrocyte. Pflugers Arch 447:121–125
Hughes FM Jr, Cidlowski JA (1999) Potassium is a critical regulator of apoptotic enzymes in vitro and in vivo. Adv Enzyme Regul 39:157–171
Remillard CV, Yuan JX (2004) Activation of K+ channels: an essential pathway in programmed cell death. Am J Physiol 286:L46–L67
Szabo I, Gulbins E, Apfel H, Zhang X, Barth P, Busch AE, Schlottmann K, Pongs O, Lang F (1996) Tyrosine phosphorylation-dependent suppression of a voltage-gated K+ channel in T lymphocytes upon Fas stimulation. J Biol Chem 271:20465–20469
Yu SP, Yeh CH, Sensi SL, Gwag BJ, Canzoniero LM, Ying HS, Tian M, Dugan LL, Choi DW (1997) Mediation of neuronal apoptosis by enhancement of outward potassium current. Science 278:114–117
Yu SP, Yeh CH, Gottron F, Wang X, Grabb MC, Choi DW (1999) Role of the outward delayed rectifier K+ current in ceramide-induced caspase activation and apoptosis in cultured neurons. J Neurochem 73:933–941
Yu SP, Yeh CH, Strasser U, Tian M, Choi DW (1999) NMDA receptor-mediated K+ efflux and neuronal apoptosis. Science 284:336–339
Yu SP, Farhangrazi ZS, Ying HS, Yeh CH, Choi DW (1998) Mediation of neuronal apoptosis by enhancement of outward potassium current. Neurobiol Dis 5:81–88
Wang L, Xu D, Dai W, Lu L (1999) An ultraviolet-activated K+ channel mediates apoptosis of myeloblastic leukemia cells. J Biol Chem 274:3678–3685
Lauritzen I, Zanzouri M, Honore E, Duprat F, Ehrengruber MU, Lazdunski M, Patel AJ (2003) K+-dependent cerebellar granule neuron apoptosis. Role of TASK leak K+ channels. J Biol Chem 278:32068–32076
Maeno E, IshizakiY, Kanaseki T, Hazama A, OkadaY (2000) Normotonic cell shrinkage because of disordered volume regulation is an early prerequisite to apoptosis. Proc Natl Acad Sci USA 97:9487–9492
Bortner CD, Hughes FM Jr, Cidlowski JA (1997) A primary role for K+ and Na+ efflux in the activation of apoptosis. J Biol Chem 272:32436–32442
Bortner CD, Cidlowski JA (1999) Caspase independent/dependent regulation of K+, cell shrinkage, and mitochondrial membrane potential during lymphocyte apoptosis. J Biol Chem 274:21953–21962
Liepins A, Younghusband HB (1987) A possible role for K+ channels in tumor cell injury. Membrane vesicle shedding and nuclear DNA fragmentation. Exp Cell Res 169:385–394
Lambert IH (1989) Leukotriene-D4 induced cell shrinkage in Ehrlich ascites tumor cells. J Membr Biol 108:165–176
Wible BA, Wang L, Kuryshev YA, Basu A, Haldar S, Brown AM (2002) Increased K+ efflux and apoptosis induced by the potassium channel modulatory protein KChAP/PIAS3beta in prostate cancer cells. J Biol Chem 277:17852–17862
Krick S, Platoshyn O, Sweeney M, Kim H, Yuan JX (2001) Activation of K+ channels induces apoptosis in vascular smooth muscle cells. Am J Physiol 280:C970–C979
Lang PA, Kaiser S, Myssina S, Wieder T, Lang F, Huber SM (2003) Role of Ca2+-activated K+ channels in human erythrocyte apoptosis. Am J Physiol 285:C1553–C1560
Nadeau H, McKinney S, Anderson DJ, Lester HA (2000) ROMK1 (Kir1.1) causes apoptosis and chronic silencing of hippocampal neurons. J Neurophysiol 84:1062–1075
Han H, Wang J, Zhang Y, Wang H, Wang Z (2003) HERG K+ channel conductance promotes H2O2-induced apoptosis in HEK293 cells: cellular mechanisms. Cell Physiol Biochem (In press)
Han H, Wang H, Long H, Nattel S, Wang Z (2001) Oxidative preconditioning and apoptosis in L-cells: Roles of protein kinase B and mitogen-activated protein kinases. J Biol Chem 276:26357–26364
Long H, Han H, Yang B, Wang Z (2003) Opposite cell density-dependence between spontaneous and oxidative stress-induced apoptosis in mouse fibroblast L-cells. Cell Physiol Biochem 13:401–414
Turner NA, Xia F, Azhar G, Zhang X, Liu L, Wei JY (1998) Oxidative stress induces DNA fragmentation and caspase activation via the c-jun NH2-terminal kinase pathway in H9c2 cardiac muscle cells. J Mol Cell Cardiol 30:1789–1801
Ekhterae D, Platoshyn O, Krick S, Yu Y, McDaniel SS, Yuan JX (2001) Bcl-2 decreases voltage-gated K+ channel activity and enhances survival in vascular smooth muscle cells. Am J Physiol 281:C157–C165
Ekhterae D, Platoshyn O, Zhang S, Remillard CV, Yuan JX (2003) Apoptosis repressor with caspase domain inhibits cardiomyocyte apoptosis by reducing K+ currents. Am J Physiol 284:C1405–C1410
Platoshyn O, Zhang S, McDaniel SS, Yuan JX (2002) Cytochrome c activates K+ channels before inducing apoptosis. Am J Physiol 283:C1298–1305
Gantner F, Uhlig S, Wendel A (1995) Quinine inhibits release of tumor necrosis factor, apoptosis, necrosis and mortality in a murine model of septic liver failure. Eur J Pharmacol 294:353–355
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Wang, Z. Roles of K+ channels in regulating tumour cell proliferation and apoptosis. Pflugers Arch - Eur J Physiol 448, 274–286 (2004). https://doi.org/10.1007/s00424-004-1258-5
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00424-004-1258-5