Abstract
We previously have reported that the activity of a 240 pS K+ channel varies during the cell cycle in pre-implantation mouse embryos. In the present study, we show that: (i) the cycling of channel activity is not prevented by inhibiting protein synthesis and hence does not involve cyclin-dependent kinase 1 (cdk1)-cyclin B; and (ii) the cycling of channel activity continues in anucleate zygote fragments with a time course similar to that observed in nucleate fragments. We further demonstrate that: (i) persistent activation of the K+ channel in one-cell embryos arrested in metaphase requires the maintenance of an active cdk1-cyclin B complex; and (ii) both DNA synthesis inhibition with aphidicolin and DNA damage produced by mitomycin C prevent the down-regulation of the channel at the start of S phase by a mechanism that requires tyrosine kinase activation. Thus, the 240 pS K+ channel in these cells is controlled by a previously unsuspected cytoplasmic clock that functions independently of the well-known clock controlling the chromosomal cell cycle, but can interact with it.
Full Text
The Full Text of this article is available as a PDF (394.9 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Amigorena S., Choquet D., Teillaud J. L., Korn H., Fridman W. H. Ion channel blockers inhibit B cell activation at a precise stage of the G1 phase of the cell cycle. Possible involvement of K+ channels. J Immunol. 1990 Mar 15;144(6):2038–2045. [PubMed] [Google Scholar]
- Arcangeli A., Bianchi L., Becchetti A., Faravelli L., Coronnello M., Mini E., Olivotto M., Wanke E. A novel inward-rectifying K+ current with a cell-cycle dependence governs the resting potential of mammalian neuroblastoma cells. J Physiol. 1995 Dec 1;489(Pt 2):455–471. doi: 10.1113/jphysiol.1995.sp021065. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Berdiev B. K., Prat A. G., Cantiello H. F., Ausiello D. A., Fuller C. M., Jovov B., Benos D. J., Ismailov I. I. Regulation of epithelial sodium channels by short actin filaments. J Biol Chem. 1996 Jul 26;271(30):17704–17710. doi: 10.1074/jbc.271.30.17704. [DOI] [PubMed] [Google Scholar]
- Block M. L., Moody W. J. A voltage-dependent chloride current linked to the cell cycle in ascidian embryos. Science. 1990 Mar 2;247(4946):1090–1092. doi: 10.1126/science.2309122. [DOI] [PubMed] [Google Scholar]
- Bregestovski P., Medina I., Goyda E. Regulation of potassium conductance in the cellular membrane at early embryogenesis. J Physiol Paris. 1992;86(1-3):109–115. doi: 10.1016/s0928-4257(05)80014-2. [DOI] [PubMed] [Google Scholar]
- Brent L. H., Butler J. L., Woods W. T., Jr, Bubien J. K. Transmembrane ion conductance in human B lymphocyte activation. J Immunol. 1990 Oct 15;145(8):2381–2389. [PubMed] [Google Scholar]
- Brüggemann A., Stühmer W., Pardo L. A. Mitosis-promoting factor-mediated suppression of a cloned delayed rectifier potassium channel expressed in Xenopus oocytes. Proc Natl Acad Sci U S A. 1997 Jan 21;94(2):537–542. doi: 10.1073/pnas.94.2.537. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Carr A. M., Hoekstra M. F. The cellular responses to DNA damage. Trends Cell Biol. 1995 Jan;5(1):32–40. doi: 10.1016/s0962-8924(00)88934-5. [DOI] [PubMed] [Google Scholar]
- Chandy K. G., DeCoursey T. E., Cahalan M. D., McLaughlin C., Gupta S. Voltage-gated potassium channels are required for human T lymphocyte activation. J Exp Med. 1984 Aug 1;160(2):369–385. doi: 10.1084/jem.160.2.369. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chatot C. L., Ziomek C. A., Bavister B. D., Lewis J. L., Torres I. An improved culture medium supports development of random-bred 1-cell mouse embryos in vitro. J Reprod Fertil. 1989 Jul;86(2):679–688. doi: 10.1530/jrf.0.0860679. [DOI] [PubMed] [Google Scholar]
- Ciapa B., Pesando D., Wilding M., Whitaker M. Cell-cycle calcium transients driven by cyclic changes in inositol trisphosphate levels. Nature. 1994 Apr 28;368(6474):875–878. doi: 10.1038/368875a0. [DOI] [PubMed] [Google Scholar]
- Ciemerych M. A. Chromatin condensation activity and cortical activity during the first three cell cycles of a mouse embryo. Mol Reprod Dev. 1995 Aug;41(4):416–424. doi: 10.1002/mrd.1080410404. [DOI] [PubMed] [Google Scholar]
- D'Souza T., Dryer S. E. A cationic channel regulated by a vertebrate intrinsic circadian oscillator. Nature. 1996 Jul 11;382(6587):165–167. doi: 10.1038/382165a0. [DOI] [PubMed] [Google Scholar]
- Day M. L., Pickering S. J., Johnson M. H., Cook D. I. Cell-cycle control of a large-conductance K+ channel in mouse early embryos. Nature. 1993 Oct 7;365(6446):560–562. doi: 10.1038/365560a0. [DOI] [PubMed] [Google Scholar]
- Dinudom A., Poronnik P., Allen D. G., Young J. A., Cook D. I. Control of intracellular Ca2+ by adrenergic and muscarinic agonists in mouse mandibular ducts and end-pieces. Cell Calcium. 1993 Oct;14(9):631–638. doi: 10.1016/0143-4160(93)90088-n. [DOI] [PubMed] [Google Scholar]
- Dubois J. M., Rouzaire-Dubois B. Role of potassium channels in mitogenesis. Prog Biophys Mol Biol. 1993;59(1):1–21. doi: 10.1016/0079-6107(93)90005-5. [DOI] [PubMed] [Google Scholar]
- Edgecombe M., Patel R., Whitaker M. A cyclin-abundance cycle-independent p34cdc2 tyrosine phosphorylation cycle in early sea urchin embryos. EMBO J. 1991 Dec;10(12):3769–3775. doi: 10.1002/j.1460-2075.1991.tb04946.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Elledge S. J., Harper J. W. Cdk inhibitors: on the threshold of checkpoints and development. Curr Opin Cell Biol. 1994 Dec;6(6):847–852. doi: 10.1016/0955-0674(94)90055-8. [DOI] [PubMed] [Google Scholar]
- Fisher R. P. CDKs and cyclins in transition(s). Curr Opin Genet Dev. 1997 Feb;7(1):32–38. doi: 10.1016/s0959-437x(97)80106-2. [DOI] [PubMed] [Google Scholar]
- Fulton B. P., Whittingham D. G. Activation of mammalian oocytes by intracellular injection of calcium. Nature. 1978 May 11;273(5658):149–151. doi: 10.1038/273149a0. [DOI] [PubMed] [Google Scholar]
- Gibb C. A., Poronnik P., Day M. L., Cook D. I. Control of cytosolic pH in two-cell mouse embryos: roles of H(+)-lactate cotransport and Na+/H+ exchange. Am J Physiol. 1997 Aug;273(2 Pt 1):C404–C419. doi: 10.1152/ajpcell.1997.273.2.C404. [DOI] [PubMed] [Google Scholar]
- Grynkiewicz G., Poenie M., Tsien R. Y. A new generation of Ca2+ indicators with greatly improved fluorescence properties. J Biol Chem. 1985 Mar 25;260(6):3440–3450. [PubMed] [Google Scholar]
- Hansen R., Oren M. p53; from inductive signal to cellular effect. Curr Opin Genet Dev. 1997 Feb;7(1):46–51. doi: 10.1016/s0959-437x(97)80108-6. [DOI] [PubMed] [Google Scholar]
- Hara K., Tydeman P., Kirschner M. A cytoplasmic clock with the same period as the division cycle in Xenopus eggs. Proc Natl Acad Sci U S A. 1980 Jan;77(1):462–466. doi: 10.1073/pnas.77.1.462. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hartwell L. H., Kastan M. B. Cell cycle control and cancer. Science. 1994 Dec 16;266(5192):1821–1828. doi: 10.1126/science.7997877. [DOI] [PubMed] [Google Scholar]
- Howlett S. K. A set of proteins showing cell cycle dependent modification in the early mouse embryo. Cell. 1986 May 9;45(3):387–396. doi: 10.1016/0092-8674(86)90324-7. [DOI] [PubMed] [Google Scholar]
- Ismailov I. I., Berdiev B. K., Shlyonsky V. G., Fuller C. M., Prat A. G., Jovov B., Cantiello H. F., Ausiello D. A., Benos D. J. Role of actin in regulation of epithelial sodium channels by CFTR. Am J Physiol. 1997 Apr;272(4 Pt 1):C1077–C1086. doi: 10.1152/ajpcell.1997.272.4.C1077. [DOI] [PubMed] [Google Scholar]
- Kharbanda S., Ren R., Pandey P., Shafman T. D., Feller S. M., Weichselbaum R. R., Kufe D. W. Activation of the c-Abl tyrosine kinase in the stress response to DNA-damaging agents. Nature. 1995 Aug 31;376(6543):785–788. doi: 10.1038/376785a0. [DOI] [PubMed] [Google Scholar]
- Kharbanda S., Yuan Z. M., Taneja N., Weichselbaum R., Kufe D. p56/p53lyn tyrosine kinase activation in mammalian cells treated with mitomycin C. Oncogene. 1994 Oct;9(10):3005–3011. [PubMed] [Google Scholar]
- Krauss R. D., Bubien J. K., Drumm M. L., Zheng T., Peiper S. C., Collins F. S., Kirk K. L., Frizzell R. A., Rado T. A. Transfection of wild-type CFTR into cystic fibrosis lymphocytes restores chloride conductance at G1 of the cell cycle. EMBO J. 1992 Mar;11(3):875–883. doi: 10.1002/j.1460-2075.1992.tb05125.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kubiak J. Z., Weber M., de Pennart H., Winston N. J., Maro B. The metaphase II arrest in mouse oocytes is controlled through microtubule-dependent destruction of cyclin B in the presence of CSF. EMBO J. 1993 Oct;12(10):3773–3778. doi: 10.1002/j.1460-2075.1993.tb06055.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Leonard R. J., Garcia M. L., Slaughter R. S., Reuben J. P. Selective blockers of voltage-gated K+ channels depolarize human T lymphocytes: mechanism of the antiproliferative effect of charybdotoxin. Proc Natl Acad Sci U S A. 1992 Nov 1;89(21):10094–10098. doi: 10.1073/pnas.89.21.10094. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lepple-Wienhues A., Berweck S., Böhmig M., Leo C. P., Meyling B., Garbe C., Wiederholt M. K+ channels and the intracellular calcium signal in human melanoma cell proliferation. J Membr Biol. 1996 May;151(2):149–157. doi: 10.1007/s002329900066. [DOI] [PubMed] [Google Scholar]
- Levy J. B., Johnson M. H., Goodall H., Maro B. The timing of compaction: control of a major developmental transition in mouse early embryogenesis. J Embryol Exp Morphol. 1986 Jun;95:213–237. [PubMed] [Google Scholar]
- Medina I. R., Bregestovski P. D. Stretch-activated ion channels modulate the resting membrane potential during early embryogenesis. Proc R Soc Lond B Biol Sci. 1988 Oct 22;235(1278):95–102. doi: 10.1098/rspb.1988.0064. [DOI] [PubMed] [Google Scholar]
- Medina I., Bregestovski P. Sensitivity of stretch-activated K+ channels changes during cell-cleavage cycle and may be regulated by cAMP-dependent protein kinase. Proc Biol Sci. 1991 Sep 23;245(1314):159–164. doi: 10.1098/rspb.1991.0103. [DOI] [PubMed] [Google Scholar]
- Michel S., Geusz M. E., Zaritsky J. J., Block G. D. Circadian rhythm in membrane conductance expressed in isolated neurons. Science. 1993 Jan 8;259(5092):239–241. doi: 10.1126/science.8421785. [DOI] [PubMed] [Google Scholar]
- Moos J., Kopf G. S., Schultz R. M. Cycloheximide-induced activation of mouse eggs: effects on cdc2/cyclin B and MAP kinase activities. J Cell Sci. 1996 Apr;109(Pt 4):739–748. doi: 10.1242/jcs.109.4.739. [DOI] [PubMed] [Google Scholar]
- Moos J., Visconti P. E., Moore G. D., Schultz R. M., Kopf G. S. Potential role of mitogen-activated protein kinase in pronuclear envelope assembly and disassembly following fertilization of mouse eggs. Biol Reprod. 1995 Sep;53(3):692–699. doi: 10.1095/biolreprod53.3.692. [DOI] [PubMed] [Google Scholar]
- Nigg E. A. Cyclin-dependent protein kinases: key regulators of the eukaryotic cell cycle. Bioessays. 1995 Jun;17(6):471–480. doi: 10.1002/bies.950170603. [DOI] [PubMed] [Google Scholar]
- Nilius B., Schwarz G., Droogmans G. Control of intracellular calcium by membrane potential in human melanoma cells. Am J Physiol. 1993 Dec;265(6 Pt 1):C1501–C1510. doi: 10.1152/ajpcell.1993.265.6.C1501. [DOI] [PubMed] [Google Scholar]
- Nilius B., Wohlrab W. Potassium channels and regulation of proliferation of human melanoma cells. J Physiol. 1992 Jan;445:537–548. doi: 10.1113/jphysiol.1992.sp018938. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pendergast A. M. Nuclear tyrosine kinases: from Abl to WEE1. Curr Opin Cell Biol. 1996 Apr;8(2):174–181. doi: 10.1016/s0955-0674(96)80063-9. [DOI] [PubMed] [Google Scholar]
- Sanguinetti M. C., Jiang C., Curran M. E., Keating M. T. A mechanistic link between an inherited and an acquired cardiac arrhythmia: HERG encodes the IKr potassium channel. Cell. 1995 Apr 21;81(2):299–307. doi: 10.1016/0092-8674(95)90340-2. [DOI] [PubMed] [Google Scholar]
- Shinagawa A. The interval of the cytoplasmic cycle observed in non-nucleate egg fragments is longer than that of the cleavage cycle in normal eggs of Xenopus laevis. J Cell Sci. 1983 Nov;64:147–162. doi: 10.1242/jcs.64.1.147. [DOI] [PubMed] [Google Scholar]
- Smith P. L., Baukrowitz T., Yellen G. The inward rectification mechanism of the HERG cardiac potassium channel. Nature. 1996 Feb 29;379(6568):833–836. doi: 10.1038/379833a0. [DOI] [PubMed] [Google Scholar]
- Strobl J. S., Wonderlin W. F., Flynn D. C. Mitogenic signal transduction in human breast cancer cells. Gen Pharmacol. 1995 Dec;26(8):1643–1649. doi: 10.1016/0306-3623(95)00062-3. [DOI] [PubMed] [Google Scholar]
- Takahashi A., Yamaguchi H., Miyamoto H. Change in K+ current of HeLa cells with progression of the cell cycle studied by patch-clamp technique. Am J Physiol. 1993 Aug;265(2 Pt 1):C328–C336. doi: 10.1152/ajpcell.1993.265.2.C328. [DOI] [PubMed] [Google Scholar]
- Tarkowki A. K. In vitro development of haploid mouse embryos produced by bisection of one-cell fertilized eggs. J Embryol Exp Morphol. 1977 Apr;38:187–202. [PubMed] [Google Scholar]
- Trudeau M. C., Warmke J. W., Ganetzky B., Robertson G. A. HERG, a human inward rectifier in the voltage-gated potassium channel family. Science. 1995 Jul 7;269(5220):92–95. doi: 10.1126/science.7604285. [DOI] [PubMed] [Google Scholar]
- Verheugen J. A., Vijverberg H. P. Intracellular Ca2+ oscillations and membrane potential fluctuations in intact human T lymphocytes: role of K+ channels in Ca2+ signaling. Cell Calcium. 1995 Apr;17(4):287–300. doi: 10.1016/0143-4160(95)90075-6. [DOI] [PubMed] [Google Scholar]
- Villaz M., Cinniger J. C., Moody W. J. A voltage-gated chloride channel in ascidian embryos modulated by both the cell cycle clock and cell volume. J Physiol. 1995 Nov 1;488(Pt 3):689–699. doi: 10.1113/jphysiol.1995.sp021000. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Waksmundzka M., Krysiak E., Karasiewicz J., Czołowska R., Tarkowski A. K. Autonomous cortical activity in mouse eggs controlled by a cytoplasmic clock. J Embryol Exp Morphol. 1984 Feb;79:77–96. [PubMed] [Google Scholar]
- Wei H., Cai Q., Rahn R. O. Inhibition of UV light- and Fenton reaction-induced oxidative DNA damage by the soybean isoflavone genistein. Carcinogenesis. 1996 Jan;17(1):73–77. doi: 10.1093/carcin/17.1.73. [DOI] [PubMed] [Google Scholar]
- Winston N. J., Johnson M. H., Braude P. R. Assessment of the cellular DNA content of whole mounted mouse and human oocytes and of blastomeres containing single or multiple nuclei. Zygote. 1993 Feb;1(1):17–25. doi: 10.1017/s0967199400001258. [DOI] [PubMed] [Google Scholar]
- Winston N. J., McGuinness O., Johnson M. H., Maro B. The exit of mouse oocytes from meiotic M-phase requires an intact spindle during intracellular calcium release. J Cell Sci. 1995 Jan;108(Pt 1):143–151. doi: 10.1242/jcs.108.1.143. [DOI] [PubMed] [Google Scholar]
- Wonderlin W. F., Strobl J. S. Potassium channels, proliferation and G1 progression. J Membr Biol. 1996 Nov;154(2):91–107. doi: 10.1007/s002329900135. [DOI] [PubMed] [Google Scholar]
- Woodfork K. A., Wonderlin W. F., Peterson V. A., Strobl J. S. Inhibition of ATP-sensitive potassium channels causes reversible cell-cycle arrest of human breast cancer cells in tissue culture. J Cell Physiol. 1995 Feb;162(2):163–171. doi: 10.1002/jcp.1041620202. [DOI] [PubMed] [Google Scholar]
- Xu B., Wilson B. A., Lu L. Induction of human myeloblastic ML-1 cell G1 arrest by suppression of K+ channel activity. Am J Physiol. 1996 Dec;271(6 Pt 1):C2037–C2044. doi: 10.1152/ajpcell.1996.271.6.C2037. [DOI] [PubMed] [Google Scholar]
- Yoneda M., Kobayakawa Y., Kubota H. Y., Sakai M. Surface contraction waves in amphibian eggs. J Cell Sci. 1982 Apr;54:35–46. doi: 10.1242/jcs.54.1.35. [DOI] [PubMed] [Google Scholar]
