Skip to main content
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1992 Mar 15;89(6):2466–2470. doi: 10.1073/pnas.89.6.2466

Extracellular K+ specifically modulates a rat brain K+ channel.

L A Pardo 1, S H Heinemann 1, H Terlau 1, U Ludewig 1, C Lorra 1, O Pongs 1, W Stühmer 1
PMCID: PMC48679  PMID: 1549610

Abstract

Extracellular potassium concentration is actively maintained within narrow limits in all higher organisms. Slight variations in extracellular potassium levels can induce major alterations of essential physiological functions in excitable tissues. Here we describe that superfusion of cultured rat hippocampal neurones with potassium-free medium leads to a decrease of a specific outward potassium current, probably carried by RCK4-type channels (RCK4 are potassium channels found in rat brain). This is confirmed by heterologous expression of these channels in Xenopus oocytes. In this system, variations of extracellular potassium in the physiological concentration range induce significant differences in current amplitude. Moreover, the current is completely suppressed in the absence of extracellular potassium. The potassium dependence of macroscopic conductance in RCK4 channels was related by site-directed mutagenesis to that lysine residue in the extracellular loop between the transmembrane segments S5 and S6 of RCK4 protein that confers resistance to extracellular blockage by tetraethylammonium. It is shown that extracellular potassium affects the number of available RCK4 channels, but not the single-channel conductance, the mean open time, or the gating charge displacement upon depolarization.

Full text

PDF
2466

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Almers W., Armstrong C. M. Survival of K+ permeability and gating currents in squid axons perfused with K+-free media. J Gen Physiol. 1980 Jan;75(1):61–78. doi: 10.1085/jgp.75.1.61. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Armstrong C. M. Interaction of tetraethylammonium ion derivatives with the potassium channels of giant axons. J Gen Physiol. 1971 Oct;58(4):413–437. doi: 10.1085/jgp.58.4.413. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Beckh S., Pongs O. Members of the RCK potassium channel family are differentially expressed in the rat nervous system. EMBO J. 1990 Mar;9(3):777–782. doi: 10.1002/j.1460-2075.1990.tb08173.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Busch A. E., Hurst R. S., North R. A., Adelman J. P., Kavanaugh M. P. Current inactivation involves a histidine residue in the pore of the rat lymphocyte potassium channel RGK5. Biochem Biophys Res Commun. 1991 Sep 30;179(3):1384–1390. doi: 10.1016/0006-291x(91)91726-s. [DOI] [PubMed] [Google Scholar]
  5. Carmeliet E. K+ channels in cardiac cells: mechanisms of activation, inactivation, rectification and K+e sensitivity. Pflugers Arch. 1989;414 (Suppl 1):S88–S92. doi: 10.1007/BF00582254. [DOI] [PubMed] [Google Scholar]
  6. Connor J. A., Stevens C. F. Voltage clamp studies of a transient outward membrane current in gastropod neural somata. J Physiol. 1971 Feb;213(1):21–30. doi: 10.1113/jphysiol.1971.sp009365. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Fozzard H. A., Makielski J. C. The electrophysiology of acute myocardial ischemia. Annu Rev Med. 1985;36:275–284. doi: 10.1146/annurev.me.36.020185.001423. [DOI] [PubMed] [Google Scholar]
  8. Grupe A., Schröter K. H., Ruppersberg J. P., Stocker M., Drewes T., Beckh S., Pongs O. Cloning and expression of a human voltage-gated potassium channel. A novel member of the RCK potassium channel family. EMBO J. 1990 Jun;9(6):1749–1756. doi: 10.1002/j.1460-2075.1990.tb08299.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Heinemann S. H., Conti F. Nonstationary noise analysis and application to patch clamp recordings. Methods Enzymol. 1992;207:131–148. doi: 10.1016/0076-6879(92)07009-d. [DOI] [PubMed] [Google Scholar]
  10. Heinemann U., Konnerth A., Pumain R., Wadman W. J. Extracellular calcium and potassium concentration changes in chronic epileptic brain tissue. Adv Neurol. 1986;44:641–661. [PubMed] [Google Scholar]
  11. Hoshi T., Zagotta W. N., Aldrich R. W. Biophysical and molecular mechanisms of Shaker potassium channel inactivation. Science. 1990 Oct 26;250(4980):533–538. doi: 10.1126/science.2122519. [DOI] [PubMed] [Google Scholar]
  12. Kamb A., Tseng-Crank J., Tanouye M. A. Multiple products of the Drosophila Shaker gene may contribute to potassium channel diversity. Neuron. 1988 Jul;1(5):421–430. doi: 10.1016/0896-6273(88)90192-4. [DOI] [PubMed] [Google Scholar]
  13. Lauritzen M., Rice M. E., Okada Y., Nicholson C. Quisqualate, kainate and NMDA can initiate spreading depression in the turtle cerebellum. Brain Res. 1988 Dec 20;475(2):317–327. doi: 10.1016/0006-8993(88)90620-8. [DOI] [PubMed] [Google Scholar]
  14. MacKinnon R., Yellen G. Mutations affecting TEA blockade and ion permeation in voltage-activated K+ channels. Science. 1990 Oct 12;250(4978):276–279. doi: 10.1126/science.2218530. [DOI] [PubMed] [Google Scholar]
  15. Methfessel C., Witzemann V., Takahashi T., Mishina M., Numa S., Sakmann B. Patch clamp measurements on Xenopus laevis oocytes: currents through endogenous channels and implanted acetylcholine receptor and sodium channels. Pflugers Arch. 1986 Dec;407(6):577–588. doi: 10.1007/BF00582635. [DOI] [PubMed] [Google Scholar]
  16. Pak M. D., Baker K., Covarrubias M., Butler A., Ratcliffe A., Salkoff L. mShal, a subfamily of A-type K+ channel cloned from mammalian brain. Proc Natl Acad Sci U S A. 1991 May 15;88(10):4386–4390. doi: 10.1073/pnas.88.10.4386. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Pongs O., Kecskemethy N., Müller R., Krah-Jentgens I., Baumann A., Kiltz H. H., Canal I., Llamazares S., Ferrus A. Shaker encodes a family of putative potassium channel proteins in the nervous system of Drosophila. EMBO J. 1988 Apr;7(4):1087–1096. doi: 10.1002/j.1460-2075.1988.tb02917.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Rice M. E., Nicholson C. Behavior of extracellular K+ and pH in skate (Raja erinacea) cerebellum. Brain Res. 1988 Oct 4;461(2):328–334. doi: 10.1016/0006-8993(88)90263-6. [DOI] [PubMed] [Google Scholar]
  19. Roberds S. L., Tamkun M. M. Cloning and tissue-specific expression of five voltage-gated potassium channel cDNAs expressed in rat heart. Proc Natl Acad Sci U S A. 1991 Mar 1;88(5):1798–1802. doi: 10.1073/pnas.88.5.1798. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Rudy B. Diversity and ubiquity of K channels. Neuroscience. 1988 Jun;25(3):729–749. doi: 10.1016/0306-4522(88)90033-4. [DOI] [PubMed] [Google Scholar]
  21. Ruppersberg J. P., Schröter K. H., Sakmann B., Stocker M., Sewing S., Pongs O. Heteromultimeric channels formed by rat brain potassium-channel proteins. Nature. 1990 Jun 7;345(6275):535–537. doi: 10.1038/345535a0. [DOI] [PubMed] [Google Scholar]
  22. Ruppersberg J. P., Stocker M., Pongs O., Heinemann S. H., Frank R., Koenen M. Regulation of fast inactivation of cloned mammalian IK(A) channels by cysteine oxidation. Nature. 1991 Aug 22;352(6337):711–714. doi: 10.1038/352711a0. [DOI] [PubMed] [Google Scholar]
  23. Schröter K. H., Ruppersberg J. P., Wunder F., Rettig J., Stocker M., Pongs O. Cloning and functional expression of a TEA-sensitive A-type potassium channel from rat brain. FEBS Lett. 1991 Jan 28;278(2):211–216. doi: 10.1016/0014-5793(91)80119-n. [DOI] [PubMed] [Google Scholar]
  24. Sigworth F. J. The variance of sodium current fluctuations at the node of Ranvier. J Physiol. 1980 Oct;307:97–129. doi: 10.1113/jphysiol.1980.sp013426. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Stocker M., Pongs O., Hoth M., Heinemann S. H., Stühmer W., Schröter K. H., Ruppersberg J. P. Swapping of functional domains in voltage-gated K+ channels. Proc Biol Sci. 1991 Aug 22;245(1313):101–107. doi: 10.1098/rspb.1991.0094. [DOI] [PubMed] [Google Scholar]
  26. Stühmer W., Conti F., Stocker M., Pongs O., Heinemann S. H. Gating currents of inactivating and non-inactivating potassium channels expressed in Xenopus oocytes. Pflugers Arch. 1991 May;418(4):423–429. doi: 10.1007/BF00550881. [DOI] [PubMed] [Google Scholar]
  27. Stühmer W., Ruppersberg J. P., Schröter K. H., Sakmann B., Stocker M., Giese K. P., Perschke A., Baumann A., Pongs O. Molecular basis of functional diversity of voltage-gated potassium channels in mammalian brain. EMBO J. 1989 Nov;8(11):3235–3244. doi: 10.1002/j.1460-2075.1989.tb08483.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Stühmer W., Stocker M., Sakmann B., Seeburg P., Baumann A., Grupe A., Pongs O. Potassium channels expressed from rat brain cDNA have delayed rectifier properties. FEBS Lett. 1988 Dec 19;242(1):199–206. doi: 10.1016/0014-5793(88)81015-9. [DOI] [PubMed] [Google Scholar]
  29. Timpe L. C., Schwarz T. L., Tempel B. L., Papazian D. M., Jan Y. N., Jan L. Y. Expression of functional potassium channels from Shaker cDNA in Xenopus oocytes. Nature. 1988 Jan 14;331(6152):143–145. doi: 10.1038/331143a0. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES