Logo of jphysiolThe Journal of Physiology SiteMembershipSubmissionJ Physiol
J Physiol. Dec 1, 1995; 489(Pt 2): 455–471.
PMCID: PMC1156772

A novel inward-rectifying K+ current with a cell-cycle dependence governs the resting potential of mammalian neuroblastoma cells.


1. Human and murine neuroblastoma cell lines were used to investigate, by the whole-cell patch-clamp technique, the properties of a novel inward-rectifying K+ current (IIR) in the adjustment of cell resting potential (Vrest), which was in the range -40 to -20 mV. 2. When elicited from a holding potential of 0 mV, IIR was completely inactivated with time constants ranging from 13 ms at -140 mV to 4.5 s at -50 mV. The steady-state inactivation curve (h(V)) was found to be independent of [Na+]o and [K+]o (2-80 mM) and could be fitted to a Boltzmann curve with a steep slope factor of 5-6, and a V1/2 around Vrest. Divalent ion-free extracellular solutions shifted h(V) to the left by about 28 mV. 3. Peak chord conductance, whose maximal value was approximately proportional to the square root of [K+]o, could be fitted to a Boltzmann curve independently of [K+]o, with a V1/2 value around -48 mV and a slope factor of 18. Extracellular Cs+ and Ba2+ blocked the IIR in a concentration- and voltage-dependent manner, but Ba2+ was less effective than it is on classical inward-rectifier channels. 4. Under control culture conditions the values of Vrest and V1/2 of h(V) varied widely among cells. The knowledge of V1/2 proved crucial or the theoretical prediction of Vrest. After cell synchronization in the G0-G1 phase of the cell cycle, or at the G1-S boundaries, the cells reduced their variability of h(V). The same occurred after cell synchronization in G1 by treatment with retinoic acid. 5. The experimental data could be fitted to a classical model of an inward rectifier, after removing the dependence of conductance activation on (V-EK), and incorporating an inactivation with an intrinsic voltage dependence. Moreover, the model predicts, for this novel inward rectifier and in contrast with the classical inward rectifier, the incapacity of maintaining, in physiological media, a Vrest more negative than -35 to -40 mV, which is an important feature of cancer cells.

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  • Arcangeli A, Becchetti A, Mannini A, Mugnai G, De Filippi P, Tarone G, Del Bene MR, Barletta E, Wanke E, Olivotto M. Integrin-mediated neurite outgrowth in neuroblastoma cells depends on the activation of potassium channels. J Cell Biol. 1993 Sep;122(5):1131–1143. [PMC free article] [PubMed]
  • Barros F, Villalobos C, García-Sancho J, del Camino D, de la Peña P. The role of the inwardly rectifying K+ current in resting potential and thyrotropin-releasing-hormone-induced changes in cell excitability of GH3 rat anterior pituitary cells. Pflugers Arch. 1994 Feb;426(3-4):221–230. [PubMed]
  • Bauer CK, Meyerhof W, Schwarz JR. An inward-rectifying K+ current in clonal rat pituitary cells and its modulation by thyrotrophin-releasing hormone. J Physiol. 1990 Oct;429:169–189. [PMC free article] [PubMed]
  • Belluzzi O, Sacchi O, Wanke E. A fast transient outward current in the rat sympathetic neurone studied under voltage-clamp conditions. J Physiol. 1985 Jan;358:91–108. [PMC free article] [PubMed]
  • Biermans G, Vereecke J, Carmeliet E. The mechanism of the inactivation of the inward-rectifying K current during hyperpolarizing steps in guinea-pig ventricular myocytes. Pflugers Arch. 1987 Dec;410(6):604–613. [PubMed]
  • Binggeli R, Weinstein RC. Membrane potentials and sodium channels: hypotheses for growth regulation and cancer formation based on changes in sodium channels and gap junctions. J Theor Biol. 1986 Dec 21;123(4):377–401. [PubMed]
  • Byerly L, Masuda MO. Voltage-clamp analysis of the potassium current that produces a negative-going action potential in Ascaris muscle. J Physiol. 1979 Mar;288:263–284. [PMC free article] [PubMed]
  • Chang HL, Baserga R. Time of replication of genes responsible for a temperature-sensitive function in a cell cycle-specific ts mutant from a hamster cell line. J Cell Physiol. 1977 Sep;92(3):333–343. [PubMed]
  • Ciani S, Krasne S, Miyazaki S, Hagiwara S. A model for anomalous rectification: electrochemical-potential-dependent gating of membrane channels. J Membr Biol. 1978 Dec 15;44(2):103–134. [PubMed]
  • Constanti A, Galvan M. Fast inward-rectifying current accounts for anomalous rectification in olfactory cortex neurones. J Physiol. 1983 Feb;335:153–178. [PMC free article] [PubMed]
  • Day ML, Pickering SJ, Johnson MH, Cook DI. Cell-cycle control of a large-conductance K+ channel in mouse early embryos. Nature. 1993 Oct 7;365(6446):560–562. [PubMed]
  • De Loof A. The electrical dimension of cells: the cell as a miniature electrophoresis chamber. Int Rev Cytol. 1986;104:251–352. [PubMed]
  • Foehring RC, Surmeier DJ. Voltage-gated potassium currents in acutely dissociated rat cortical neurons. J Neurophysiol. 1993 Jul;70(1):51–63. [PubMed]
  • Gallin EK, Sheehy PA. Differential expression of inward and outward potassium currents in the macrophage-like cell line J774.1. J Physiol. 1985 Dec;369:475–499. [PMC free article] [PubMed]
  • Guadagno TM, Ohtsubo M, Roberts JM, Assoian RK. A link between cyclin A expression and adhesion-dependent cell cycle progression. Science. 1993 Dec 3;262(5139):1572–1575. [PubMed]
  • Hagiwara S, Takahashi K. The anomalous rectification and cation selectivity of the membrane of a starfish egg cell. J Membr Biol. 1974;18(1):61–80. [PubMed]
  • Hagiwara S, Yoshii M. Effects of internal potassium and sodium on the anomalous rectification of the starfish egg as examined by internal perfusion. J Physiol. 1979 Jul;292:251–265. [PMC free article] [PubMed]
  • Harvey RD, Ten Eick RE. Voltage-dependent block of cardiac inward-rectifying potassium current by monovalent cations. J Gen Physiol. 1989 Aug;94(2):349–361. [PMC free article] [PubMed]
  • HODGKIN AL, HUXLEY AF. Currents carried by sodium and potassium ions through the membrane of the giant axon of Loligo. J Physiol. 1952 Apr;116(4):449–472. [PMC free article] [PubMed]
  • Hynes RO. Integrins: versatility, modulation, and signaling in cell adhesion. Cell. 1992 Apr 3;69(1):11–25. [PubMed]
  • Inoue M, Yoshii M. Modulation of ion channels by somatostatin and acetylcholine. Prog Neurobiol. 1992;38(2):203–230. [PubMed]
  • Ishihara K, Mitsuiye T, Noma A, Takano M. The Mg2+ block and intrinsic gating underlying inward rectification of the K+ current in guinea-pig cardiac myocytes. J Physiol. 1989 Dec;419:297–320. [PMC free article] [PubMed]
  • Jan LY, Jan YN. Potassium channels and their evolving gates. Nature. 1994 Sep 8;371(6493):119–122. [PubMed]
  • Johnson BD, Byerly L. A cytoskeletal mechanism for Ca2+ channel metabolic dependence and inactivation by intracellular Ca2+. Neuron. 1993 May;10(5):797–804. [PubMed]
  • Kubo Y, Baldwin TJ, Jan YN, Jan LY. Primary structure and functional expression of a mouse inward rectifier potassium channel. Nature. 1993 Mar 11;362(6416):127–133. [PubMed]
  • Leech CA, Stanfield PR. Inward rectification in frog skeletal muscle fibres and its dependence on membrane potential and external potassium. J Physiol. 1981;319:295–309. [PMC free article] [PubMed]
  • Sakmann B, Trube G. Voltage-dependent inactivation of inward-rectifying single-channel currents in the guinea-pig heart cell membrane. J Physiol. 1984 Feb;347:659–683. [PMC free article] [PubMed]
  • Sherr CJ. Mammalian G1 cyclins. Cell. 1993 Jun 18;73(6):1059–1065. [PubMed]
  • Silver MR, DeCoursey TE. Intrinsic gating of inward rectifier in bovine pulmonary artery endothelial cells in the presence or absence of internal Mg2+. J Gen Physiol. 1990 Jul;96(1):109–133. [PMC free article] [PubMed]
  • Standen NB, Stanfield PR. A potential- and time-dependent blockade of inward rectification in frog skeletal muscle fibres by barium and strontium ions. J Physiol. 1978 Jul;280:169–191. [PMC free article] [PubMed]
  • Standen NB, Stanfield PR. Potassium depletion and sodium block of potassium currents under hyperpolarization in frog sartorius muscle. J Physiol. 1979 Sep;294:497–520. [PMC free article] [PubMed]
  • Thiele CJ, Reynolds CP, Israel MA. Decreased expression of N-myc precedes retinoic acid-induced morphological differentiation of human neuroblastoma. Nature. 313(6001):404–406. [PubMed]
  • van de Loosdrecht AA, Ossenkoppele GJ, Beelen RH, Broekhoven MG, Langenhuijsen MM. Cell cycle specific effects of tumor necrosis factor alpha in monocyte mediated leukemic cell death and the role of beta 2-integrins. Cancer Res. 1993 Sep 15;53(18):4399–4407. [PubMed]
  • Wanke E, Carbone E, Testa PL. The sodium channel and intracellular H+ blockage in squid axons. Nature. 1980 Sep 4;287(5777):62–63. [PubMed]
  • Warmke JW, Ganetzky B. A family of potassium channel genes related to eag in Drosophila and mammals. Proc Natl Acad Sci U S A. 1994 Apr 12;91(8):3438–3442. [PMC free article] [PubMed]

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