Pflügers Archiv

, Volume 448, Issue 3, pp 274–286 | Cite as

Roles of K+ channels in regulating tumour cell proliferation and apoptosis

  • Zhiguo Wang
Invited Review


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.


K+ channels Tumour cells Proliferation Apoptosis Cancers 


  1. 1.
    Simonneau M, Distasi C, Tauc L, Poujeol C (1985) Development of ionic channels during mouse neuronal differentiation. J Physiol (Paris) 80:312–320Google Scholar
  2. 2.
    Vyklicky L Jr, Michl J, Vlachova V, Vyklicky L, Vyskocil F (1985) Ionic currents in neuroblastoma clone E-7 cells. Neurosci Lett 55:197–201CrossRefPubMedGoogle Scholar
  3. 3.
    Lang DG, Ritchie AK (1987) Large and small conductance calcium-activated potassium channels in the GH3 anterior pituitary cell line. Pflugers Arch 410:614–622PubMedGoogle Scholar
  4. 4.
    Weiger T, Hermann A (1994) Polyamines block Ca2+-activated K+ channels in pituitary tumor cells (GH3). J Membr Biol 140:133–142PubMedGoogle Scholar
  5. 5.
    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 192:188–199CrossRefPubMedGoogle Scholar
  6. 6.
    Li ZW, Ding JP, Kalyanaraman V, Lingle CJ (1999) RINm5f cells express inactivating BK channels whereas HIT cells express noninactivating BK channels. J Neurophysiol 81:611–624PubMedGoogle Scholar
  7. 7.
    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 22:1840–1849PubMedGoogle Scholar
  8. 8.
    Basavappa S, Mangel AW, Boulpaep EL (2003) Calcium-dependent, swelling-activated K+ conductance in human neuroblastoma cells. Biochem Biophys Res Commun 308:759–763CrossRefPubMedGoogle Scholar
  9. 9.
    Quandt FN (1988) Three kinetically distinct potassium channels in mouse neuroblastoma cells. J Physiol (Lond) 395:401–418Google Scholar
  10. 10.
    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 12:1984–1992PubMedGoogle Scholar
  11. 11.
    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–G122Google Scholar
  12. 12.
    Kraft R, Benndorf K, Patt S (2000) Large conductance Ca2+-activated K+ channels in human meningioma cells. J Membr Biol 175:25–33PubMedGoogle Scholar
  13. 13.
    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 171:107–115CrossRefPubMedGoogle Scholar
  14. 14.
    Allen DH, Lepple-Wienhues A, Cahalan MD (1997) Ion channel phenotype of melanoma cell lines. J Membr Biol 155:27–34CrossRefPubMedGoogle Scholar
  15. 15.
    Monen SH, Schmidt PH, Wondergem R (1998) Membrane potassium channels and human bladder tumor cells. I. Electrical properties. J Membr Biol 161:247–256CrossRefPubMedGoogle Scholar
  16. 16.
    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 218:745–748CrossRefPubMedGoogle Scholar
  17. 17.
    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 430:534–540PubMedGoogle Scholar
  18. 18.
    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 156:341–347PubMedGoogle Scholar
  19. 19.
    Bordey A, Sontheimer H (1998) Electrophysiological properties of human astrocytic tumor cells in situ: enigma of spiking glial cells. J Neurophysiol 79:2782–2793PubMedGoogle Scholar
  20. 20.
    Cukierman S (1992) Characterization of K+ currents in rat malignant lymphocytes (Nb2 cells). J Membr Biol 126:147–157PubMedGoogle Scholar
  21. 21.
    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 6:241–253PubMedGoogle Scholar
  22. 22.
    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–L716PubMedGoogle Scholar
  23. 23.
    Hoshi T, Aldrich RW (1988) Voltage-dependent K+ currents and underlying single K+ channels in pheochromocytoma cells. J Gen Physiol 91:73–106PubMedGoogle Scholar
  24. 24.
    Hoshi T, Aldrich RW (1988) Gating kinetics of four classes of voltage-dependent K+ channels in pheochromocytoma cells. J Gen Physiol 81:197–131Google Scholar
  25. 25.
    Conforti L, Millhorn DE (1997) Selective inhibition of a slow-inactivating voltage-dependent K+ channel in rat PC12 cells by hypoxia. J Physiol (Lond) 503:293–305Google Scholar
  26. 26.
    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 446:559–571CrossRefPubMedGoogle Scholar
  27. 27.
    Abdul M, Santo A, Hoosein N (2003) Activity of potassium channel-blockers in breast cancer. Anticancer Res 23:3347–3351PubMedGoogle Scholar
  28. 28.
    Zhou ZH, Unlap T, Li L, Ma HP (2002) Incomplete inactivation of voltage-dependent K+ channels in human B lymphoma cells. J Membr Biol 188:97–105CrossRefPubMedGoogle Scholar
  29. 29.
    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 346:33–36CrossRefPubMedGoogle Scholar
  30. 30.
    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 278:272–277CrossRefPubMedGoogle Scholar
  31. 31.
    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 277:20195–20204CrossRefPubMedGoogle Scholar
  32. 32.
    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 277:44938–44945CrossRefPubMedGoogle Scholar
  33. 33.
    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 442:49–56CrossRefPubMedGoogle Scholar
  34. 34.
    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 38:16984–16992CrossRefPubMedGoogle Scholar
  35. 35.
    Nobile M, Lagostena L (1998) A discriminant block among K+ channel types by phenytoin in neuroblastoma cells. Br J Pharmacol 124:1698–1702PubMedGoogle Scholar
  36. 36.
    Meyer R, Heinemann SH (1998) Characterization of an eag-like potassium channel in human neuroblastoma cells. J Physiol (Lond) 508:49–56Google Scholar
  37. 37.
    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 93:9910–9914CrossRefPubMedGoogle Scholar
  38. 38.
    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 143:767–775PubMedGoogle Scholar
  39. 39.
    Pardo LA, del Camino D, Sanchez A, Alves F, Bruggemann A, Beckh S, Stuhmer W (1999) Oncogenic potential of EAG K+ channels. EMBO J 18:5540–5547CrossRefPubMedGoogle Scholar
  40. 40.
    Bauer CK, Schwarz JR (2001) Physiology of EAG K+ channels. J Membr Biol 182:1–15PubMedGoogle Scholar
  41. 41.
    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 81:299–307PubMedGoogle Scholar
  42. 42.
    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 29:301–307CrossRefPubMedGoogle Scholar
  43. 43.
    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 80:782–789PubMedGoogle Scholar
  44. 44.
    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 73:27–32CrossRefPubMedGoogle Scholar
  45. 45.
    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 95:2979–2984CrossRefPubMedGoogle Scholar
  46. 46.
    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 62:4843–4848PubMedGoogle Scholar
  47. 47.
    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 58:815–822PubMedGoogle Scholar
  48. 48.
    Meves H (2000) Effect of low external calcium on the ERG current of NG108-15 cells. Biochim Biophys Acta 1509:245–254CrossRefPubMedGoogle Scholar
  49. 49.
    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 441:228–234CrossRefPubMedGoogle Scholar
  50. 50.
    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 40:1053–1058CrossRefPubMedGoogle Scholar
  51. 51.
    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:RC212:1–5Google Scholar
  52. 52.
    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 83:1722–1729CrossRefPubMedGoogle Scholar
  53. 53.
    Finlayson K, Pennington AJ, Kelly JS (2001) [3H]dofetilide binding in SHSY5Y and HEK293 cells expressing a HERG-like K+ channel? Eur J Pharmacol 412:203–212CrossRefPubMedGoogle Scholar
  54. 54.
    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 16:1791–1798CrossRefPubMedGoogle Scholar
  55. 55.
    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 277:18528–18534CrossRefPubMedGoogle Scholar
  56. 56.
    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 278:2947–2955CrossRefPubMedGoogle Scholar
  57. 57.
    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 445:589–600PubMedGoogle Scholar
  58. 58.
    Liu YC, Wu SN (2003) Block of erg current by linoleoylamide, a sleep-inducing agent, in pituitary GH3 cells. Eur J Pharmacol 458:37–47CrossRefPubMedGoogle Scholar
  59. 59.
    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 64:606–611PubMedGoogle Scholar
  60. 60.
    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 16:415–428CrossRefPubMedGoogle Scholar
  61. 61.
    Brismar T, Collins VP (1989) Inward rectifying potassium channels in human malignant glioma cells. Brain Res 480:249–258PubMedGoogle Scholar
  62. 62.
    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 290:17–21CrossRefPubMedGoogle Scholar
  63. 63.
    Mukai M, Takada K (1991) Ca2+-dependent suppression of inwardly rectified K+ channels in rat basophilic leukemia cells. Osaka City Med J 37:53–64PubMedGoogle Scholar
  64. 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 53:4156–4160PubMedGoogle Scholar
  65. 65.
    Collins A, German MS, Jan YN, Jan LY, Zhao B (1996) A strongly inwardly rectifying K+ channel that is sensitive to ATP. J Neurosci 16:1–9PubMedGoogle Scholar
  66. 66.
    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 210:823–829CrossRefPubMedGoogle Scholar
  67. 67.
    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 38:466–474CrossRefPubMedGoogle Scholar
  68. 68.
    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 287:53–56CrossRefPubMedGoogle Scholar
  69. 69.
    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 435:125–133CrossRefPubMedGoogle Scholar
  70. 70.
    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 85:8360–8364PubMedGoogle Scholar
  71. 71.
    Plant TD, Jonas JC, Henquin JC (1991) Clonidine inhibits ATP-sensitive K+ channels in mouse pancreatic beta-cells. Br J Pharmacol 104:385–390PubMedGoogle Scholar
  72. 72.
    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 8:413–420PubMedGoogle Scholar
  73. 73.
    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 109:123–134PubMedGoogle Scholar
  74. 74.
    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 370:179–185CrossRefPubMedGoogle Scholar
  75. 75.
    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 129:13–36PubMedGoogle Scholar
  76. 76.
    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 130:565–575Google Scholar
  77. 77.
    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 276:43166–43174PubMedGoogle Scholar
  78. 78.
    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 130:355–366CrossRefPubMedGoogle Scholar
  79. 79.
    Selyanko AA, Robbins J, Brown DA (1995) Putative M-type potassium channels in neuroblastoma-glioma hybrid cells: inhibition by muscarine and bradykinin. Receptors Channels 3:147–159PubMedGoogle Scholar
  80. 80.
    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 794:274–280CrossRefPubMedGoogle Scholar
  81. 81.
    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 90:908–912PubMedGoogle Scholar
  82. 82.
    Wang L, Xu D, Dai W, Lu L (1999) An ultraviolet-activated K+ channel mediates apoptosis of myeloblastic leukemia cells. J Biol Chem 274:3678–3685CrossRefPubMedGoogle Scholar
  83. 83.
    Rouzaire-Dubois B, Dubois JM (1990) Tamoxifen blocks both proliferation and voltage-dependent K+ channels of neuroblastoma cells. Cell Signal 2:387–393CrossRefPubMedGoogle Scholar
  84. 84.
    Pancrazio JJ, Tabbara IA, Kim YI (1993) Voltage-activated K+ conductance and cell proliferation in small-cell lung cancer. Anticancer Res 13:1231–1234PubMedGoogle Scholar
  85. 85.
    Rouzaire-Dubois B, Gerard V, Dubois JM (1993) Involvement of K+ channels in the quercetin-induced inhibition of neuroblastoma cell growth. Pflugers Arch 423:202–205PubMedGoogle Scholar
  86. 86.
    Fieber LA, Gonzalez DM, Wallace MR, Muir D (2003) Delayed rectifier K currents in NF1 Schwann cells. Pharmacological block inhibits proliferation. Neurobiol Dis 13:136–146CrossRefPubMedGoogle Scholar
  87. 87.
    Nilius B, Wohlrab W (1992) Potassium channels and regulation of proliferation of human melanoma cells. J Physiol (Lond) 445:537–548Google Scholar
  88. 88.
    Rouzaire-Dubois B, Dubois JM (1991) A quantitative analysis of the role of K+ channels in mitogenesis of neuroblastoma cells. Cell Signal 3:333–339CrossRefPubMedGoogle Scholar
  89. 89.
    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 257:184–191PubMedGoogle Scholar
  90. 90.
    Wang YF, Jia H, Walker AM, Cukierman S (1992) K-current mediation of prolactin-induced proliferation of malignant (Nb2) lymphocytes. J Cell Physiol 152:185–189PubMedGoogle Scholar
  91. 91.
    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 11:261–266PubMedGoogle Scholar
  92. 92.
    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 65:55–62CrossRefPubMedGoogle Scholar
  93. 93.
    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 33:112–122CrossRefPubMedGoogle Scholar
  94. 94.
    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 44:61–76CrossRefPubMedGoogle Scholar
  95. 95.
    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 59:1376–1387PubMedGoogle Scholar
  96. 96.
    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 377:569–578PubMedGoogle Scholar
  97. 97.
    Warmke J, Drysdale R, Ganetzky B (1991) A distinct potassium channel polypeptide encoded by the Drosophila eag locus. Science 252:1560–1562PubMedGoogle Scholar
  98. 98.
    Warmke JW, Ganetzky B (1994) A family of potassium channel genes related to eag in Drosophila and mammals. Proc Natl Acad Sci USA 91:3438–3442PubMedGoogle Scholar
  99. 99.
    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 7:345–356PubMedGoogle Scholar
  100. 100.
    Wang L, Feng ZP, Kondo CS, Sheldon RS, Duff HJ (1996) Developmental changes in the delayed rectifier K+ channels in mouse heart. Circ Res 79:79–85PubMedGoogle Scholar
  101. 101.
    Wang L, Duff HJ (1996) Identification and characteristics of delayed rectifier K+ current in fetal mouse ventricular myocytes. Am J Physiol 270:H2088–H2093PubMedGoogle Scholar
  102. 102.
    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 9:2596–2604PubMedGoogle Scholar
  103. 103.
    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 95:239–243PubMedGoogle Scholar
  104. 104.
    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 276:4923–4931CrossRefPubMedGoogle Scholar
  105. 105.
    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 151:146–157CrossRefGoogle Scholar
  106. 106.
    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 275:26050–26057PubMedGoogle Scholar
  107. 107.
    Lee YS, Sayeed MM, Wurster RD (1994) In vitro antitumor activity of cromakalim in human brain tumor cells. Pharmacology 49:69–74PubMedGoogle Scholar
  108. 108.
    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 70:1185–1203CrossRefPubMedGoogle Scholar
  109. 109.
    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 28:853–856PubMedGoogle Scholar
  110. 110.
    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 23:349–365PubMedGoogle Scholar
  111. 111.
    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 41:697–706PubMedGoogle Scholar
  112. 112.
    Binggeli R, Cameron IL (1980) Cellular potentials of normal and cancerous fibroblasts and hepatocytes. Cancer Res 40:1830–1835PubMedGoogle Scholar
  113. 113.
    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 49:4842–4845PubMedGoogle Scholar
  114. 114.
    Marino AA, Morris DM, Schwalke MA, Iliev IG, Rogers S (1994) Electrical potential measurements in human breast cancer and benign lesions Tumour Biol 15:147–152Google Scholar
  115. 115.
    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 165:177–185PubMedGoogle Scholar
  116. 116.
    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 74:48–53PubMedGoogle Scholar
  117. 117.
    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 264:12914–12921PubMedGoogle Scholar
  118. 118.
    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 266:4938–4942PubMedGoogle Scholar
  119. 119.
    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 421:416–424PubMedGoogle Scholar
  120. 120.
    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 22:81–95PubMedGoogle Scholar
  121. 121.
    Kim JA, Chung YJ, Lee YS (1998) Intracellular Ca2+ mediates lipoxygenase-induced proliferation of U-373 MG human astrocytoma cells. Arch Pharm Res 21:664–670PubMedGoogle Scholar
  122. 122.
    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 16:56–64PubMedGoogle Scholar
  123. 123.
    Rouzaire-Dubois B, Dubois JM (1998) K+ channel block-induced mammalian neuroblastoma cell swelling: a possible mechanism to influence proliferation. J Physiol (Lond) 510:93–102Google Scholar
  124. 124.
    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 171:165–172CrossRefPubMedGoogle Scholar
  125. 125.
    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–C1665PubMedGoogle Scholar
  126. 126.
    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 94:139–145Google Scholar
  127. 127.
    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 12:535–538CrossRefPubMedGoogle Scholar
  128. 128.
    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 18:471–479CrossRefPubMedGoogle Scholar
  129. 129.
    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 10:417–428PubMedGoogle Scholar
  130. 130.
    Yu SP (2003) Regulation and critical role of potassium homeostasis in apoptosis. Prog Neurobiol 70:363–386CrossRefPubMedGoogle Scholar
  131. 131.
    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 447:121–125CrossRefPubMedGoogle Scholar
  132. 132.
    Hughes FM Jr, Cidlowski JA (1999) Potassium is a critical regulator of apoptotic enzymes in vitro and in vivo. Adv Enzyme Regul 39:157–171CrossRefPubMedGoogle Scholar
  133. 133.
    Remillard CV, Yuan JX (2004) Activation of K+ channels: an essential pathway in programmed cell death. Am J Physiol 286:L46–L67Google Scholar
  134. 134.
    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 271:20465–20469PubMedGoogle Scholar
  135. 135.
    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 278:114–117PubMedGoogle Scholar
  136. 136.
    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 73:933–941CrossRefPubMedGoogle Scholar
  137. 137.
    Yu SP, Yeh CH, Strasser U, Tian M, Choi DW (1999) NMDA receptor-mediated K+ efflux and neuronal apoptosis. Science 284:336–339CrossRefPubMedGoogle Scholar
  138. 138.
    Yu SP, Farhangrazi ZS, Ying HS, Yeh CH, Choi DW (1998) Mediation of neuronal apoptosis by enhancement of outward potassium current. Neurobiol Dis 5:81–88CrossRefPubMedGoogle Scholar
  139. 139.
    Wang L, Xu D, Dai W, Lu L (1999) An ultraviolet-activated K+ channel mediates apoptosis of myeloblastic leukemia cells. J Biol Chem 274:3678–3685CrossRefPubMedGoogle Scholar
  140. 140.
    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 278:32068–32076CrossRefPubMedGoogle Scholar
  141. 141.
    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 97:9487–9492PubMedGoogle Scholar
  142. 142.
    Bortner CD, Hughes FM Jr, Cidlowski JA (1997) A primary role for K+ and Na+ efflux in the activation of apoptosis. J Biol Chem 272:32436–32442PubMedGoogle Scholar
  143. 143.
    Bortner CD, Cidlowski JA (1999) Caspase independent/dependent regulation of K+, cell shrinkage, and mitochondrial membrane potential during lymphocyte apoptosis. J Biol Chem 274:21953–21962PubMedGoogle Scholar
  144. 144.
    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 169:385–394PubMedGoogle Scholar
  145. 145.
    Lambert IH (1989) Leukotriene-D4 induced cell shrinkage in Ehrlich ascites tumor cells. J Membr Biol 108:165–176PubMedGoogle Scholar
  146. 146.
    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 277:17852–17862CrossRefPubMedGoogle Scholar
  147. 147.
    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–C979Google Scholar
  148. 148.
    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–C1560Google Scholar
  149. 149.
    Nadeau H, McKinney S, Anderson DJ, Lester HA (2000) ROMK1 (Kir1.1) causes apoptosis and chronic silencing of hippocampal neurons. J Neurophysiol 84:1062–1075PubMedGoogle Scholar
  150. 150.
    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)Google Scholar
  151. 151.
    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 276:26357–26364CrossRefPubMedGoogle Scholar
  152. 152.
    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 13:401–414CrossRefPubMedGoogle Scholar
  153. 153.
    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 30:1789–1801PubMedGoogle Scholar
  154. 154.
    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–C165Google Scholar
  155. 155.
    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–C1410Google Scholar
  156. 156.
    Platoshyn O, Zhang S, McDaniel SS, Yuan JX (2002) Cytochrome c activates K+ channels before inducing apoptosis. Am J Physiol 283:C1298–1305Google Scholar
  157. 157.
    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 294:353–355CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag  2004

Authors and Affiliations

  1. 1.Research CentreMontreal Heart InstituteMontrealCanada

Personalised recommendations