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
. 1991 May 15;88(10):4386–4390. doi: 10.1073/pnas.88.10.4386

mShal, a subfamily of A-type K+ channel cloned from mammalian brain.

M D Pak 1, K Baker 1, M Covarrubias 1, A Butler 1, A Ratcliffe 1, L Salkoff 1
PMCID: PMC51664  PMID: 2034678

Abstract

We have cloned and expressed a mouse brain cDNA, mShal, that encodes a transient, A-type K+ current. mShal, the vertebrate homolog of the Drosophila Shal gene, defines a distinct subfamily of voltage-gated K+ channels. The Shal deduced proteins are more highly conserved between mouse and Drosophila than other presently known K+ channels. mShal carries a "low-threshold" A-type current with a hyperpolarized steady-state inactivation midpoint. Marked similarity was observed between mShal and its Drosophila homolog, fShal, with regard to voltage sensitivity of activation, macroscopic inactivation, steady-state inactivation, and 4-aminopyridine sensitivity. Sequence conservation for Shal proteins is unusually high at the amino terminus, an area considered important for inactivation. Removal of conserved amino-terminal residues from mShal modifies macroscopic inactivation but the transient nature of the current is preserved. Underlying the very high conservation of mShal and fShal may be a role in the nervous system that is conserved in widely divergent species.

Full text

PDF
4388

Images in this article

Selected References

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

  1. Baker K., Salkoff L. The Drosophila Shaker gene codes for a distinctive K+ current in a subset of neurons. Neuron. 1990 Jan;4(1):129–140. doi: 10.1016/0896-6273(90)90449-p. [DOI] [PubMed] [Google Scholar]
  2. Baumann A., Grupe A., Ackermann A., Pongs O. Structure of the voltage-dependent potassium channel is highly conserved from Drosophila to vertebrate central nervous systems. EMBO J. 1988 Aug;7(8):2457–2463. doi: 10.1002/j.1460-2075.1988.tb03092.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Butler A., Wei A. G., Baker K., Salkoff L. A family of putative potassium channel genes in Drosophila. Science. 1989 Feb 17;243(4893):943–947. doi: 10.1126/science.2493160. [DOI] [PubMed] [Google Scholar]
  4. Christie M. J., Adelman J. P., Douglass J., North R. A. Expression of a cloned rat brain potassium channel in Xenopus oocytes. Science. 1989 Apr 14;244(4901):221–224. doi: 10.1126/science.2539643. [DOI] [PubMed] [Google Scholar]
  5. Connor J. A., Stevens C. F. Prediction of repetitive firing behaviour from voltage clamp data on an isolated neurone soma. J Physiol. 1971 Feb;213(1):31–53. doi: 10.1113/jphysiol.1971.sp009366. [DOI] [PMC free article] [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. Douglass J., Osborne P. B., Cai Y. C., Wilkinson M., Christie M. J., Adelman J. P. Characterization and functional expression of a rat genomic DNA clone encoding a lymphocyte potassium channel. J Immunol. 1990 Jun 15;144(12):4841–4850. [PubMed] [Google Scholar]
  8. Frech G. C., VanDongen A. M., Schuster G., Brown A. M., Joho R. H. A novel potassium channel with delayed rectifier properties isolated from rat brain by expression cloning. Nature. 1989 Aug 24;340(6235):642–645. doi: 10.1038/340642a0. [DOI] [PubMed] [Google Scholar]
  9. 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]
  10. 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]
  11. Isacoff E. Y., Jan Y. N., Jan L. Y. Evidence for the formation of heteromultimeric potassium channels in Xenopus oocytes. Nature. 1990 Jun 7;345(6275):530–534. doi: 10.1038/345530a0. [DOI] [PubMed] [Google Scholar]
  12. Iverson L. E., Rudy B. The role of the divergent amino and carboxyl domains on the inactivation properties of potassium channels derived from the Shaker gene of Drosophila. J Neurosci. 1990 Sep;10(9):2903–2916. doi: 10.1523/JNEUROSCI.10-09-02903.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Iverson L. E., Tanouye M. A., Lester H. A., Davidson N., Rudy B. A-type potassium channels expressed from Shaker locus cDNA. Proc Natl Acad Sci U S A. 1988 Aug;85(15):5723–5727. doi: 10.1073/pnas.85.15.5723. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. 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]
  15. Koren G., Liman E. R., Logothetis D. E., Nadal-Ginard B., Hess P. Gating mechanism of a cloned potassium channel expressed in frog oocytes and mammalian cells. Neuron. 1990 Jan;4(1):39–51. doi: 10.1016/0896-6273(90)90442-i. [DOI] [PubMed] [Google Scholar]
  16. Kozak M. The scanning model for translation: an update. J Cell Biol. 1989 Feb;108(2):229–241. doi: 10.1083/jcb.108.2.229. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. 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]
  18. McCormack T., Vega-Saenz de Miera E. C., Rudy B. Molecular cloning of a member of a third class of Shaker-family K+ channel genes in mammals. Proc Natl Acad Sci U S A. 1990 Jul;87(13):5227–5231. doi: 10.1073/pnas.87.13.5227. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. McKinnon D. Isolation of a cDNA clone coding for a putative second potassium channel indicates the existence of a gene family. J Biol Chem. 1989 May 15;264(14):8230–8236. [PubMed] [Google Scholar]
  20. Neher E. Two fast transient current components during voltage clamp on snail neurons. J Gen Physiol. 1971 Jul;58(1):36–53. doi: 10.1085/jgp.58.1.36. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Padgett R. A., Grabowski P. J., Konarska M. M., Seiler S., Sharp P. A. Splicing of messenger RNA precursors. Annu Rev Biochem. 1986;55:1119–1150. doi: 10.1146/annurev.bi.55.070186.005351. [DOI] [PubMed] [Google Scholar]
  22. Pak M. D., Covarrubias M., Ratcliffe A., Salkoff L. A mouse brain homolog of the Drosophila Shab K+ channel with conserved delayed-rectifier properties. J Neurosci. 1991 Mar;11(3):869–880. doi: 10.1523/JNEUROSCI.11-03-00869.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. 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]
  24. 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]
  25. Rudy B., Hoger J. H., Lester H. A., Davidson N. At least two mRNA species contribute to the properties of rat brain A-type potassium channels expressed in Xenopus oocytes. Neuron. 1988 Oct;1(8):649–658. doi: 10.1016/0896-6273(88)90164-x. [DOI] [PubMed] [Google Scholar]
  26. Saiki R. K., Gelfand D. H., Stoffel S., Scharf S. J., Higuchi R., Horn G. T., Mullis K. B., Erlich H. A. Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science. 1988 Jan 29;239(4839):487–491. doi: 10.1126/science.2448875. [DOI] [PubMed] [Google Scholar]
  27. Schwarz T. L., Tempel B. L., Papazian D. M., Jan Y. N., Jan L. Y. Multiple potassium-channel components are produced by alternative splicing at the Shaker locus in Drosophila. Nature. 1988 Jan 14;331(6152):137–142. doi: 10.1038/331137a0. [DOI] [PubMed] [Google Scholar]
  28. Solc C. K., Zagotta W. N., Aldrich R. W. Single-channel and genetic analyses reveal two distinct A-type potassium channels in Drosophila. Science. 1987 May 29;236(4805):1094–1098. doi: 10.1126/science.2437657. [DOI] [PubMed] [Google Scholar]
  29. 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]
  30. 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]
  31. Swanson R., Marshall J., Smith J. S., Williams J. B., Boyle M. B., Folander K., Luneau C. J., Antanavage J., Oliva C., Buhrow S. A. Cloning and expression of cDNA and genomic clones encoding three delayed rectifier potassium channels in rat brain. Neuron. 1990 Jun;4(6):929–939. doi: 10.1016/0896-6273(90)90146-7. [DOI] [PubMed] [Google Scholar]
  32. Tempel B. L., Jan Y. N., Jan L. Y. Cloning of a probable potassium channel gene from mouse brain. Nature. 1988 Apr 28;332(6167):837–839. doi: 10.1038/332837a0. [DOI] [PubMed] [Google Scholar]
  33. Tempel B. L., Papazian D. M., Schwarz T. L., Jan Y. N., Jan L. Y. Sequence of a probable potassium channel component encoded at Shaker locus of Drosophila. Science. 1987 Aug 14;237(4816):770–775. doi: 10.1126/science.2441471. [DOI] [PubMed] [Google Scholar]
  34. Thompson S. H. Three pharmacologically distinct potassium channels in molluscan neurones. J Physiol. 1977 Feb;265(2):465–488. doi: 10.1113/jphysiol.1977.sp011725. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Timpe L. C., Jan Y. N., Jan L. Y. Four cDNA clones from the Shaker locus of Drosophila induce kinetically distinct A-type potassium currents in Xenopus oocytes. Neuron. 1988 Oct;1(8):659–667. doi: 10.1016/0896-6273(88)90165-1. [DOI] [PubMed] [Google Scholar]
  36. 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]
  37. Tseng-Crank J. C., Tseng G. N., Schwartz A., Tanouye M. A. Molecular cloning and functional expression of a potassium channel cDNA isolated from a rat cardiac library. FEBS Lett. 1990 Jul 30;268(1):63–68. doi: 10.1016/0014-5793(90)80973-m. [DOI] [PubMed] [Google Scholar]
  38. Wei A., Covarrubias M., Butler A., Baker K., Pak M., Salkoff L. K+ current diversity is produced by an extended gene family conserved in Drosophila and mouse. Science. 1990 May 4;248(4955):599–603. doi: 10.1126/science.2333511. [DOI] [PubMed] [Google Scholar]
  39. Yokoyama S., Imoto K., Kawamura T., Higashida H., Iwabe N., Miyata T., Numa S. Potassium channels from NG108-15 neuroblastoma-glioma hybrid cells. Primary structure and functional expression from cDNAs. FEBS Lett. 1989 Dec 18;259(1):37–42. doi: 10.1016/0014-5793(89)81488-7. [DOI] [PubMed] [Google Scholar]
  40. Zagotta W. N., Aldrich R. W. Alterations in activation gating of single Shaker A-type potassium channels by the Sh5 mutation. J Neurosci. 1990 Jun;10(6):1799–1810. doi: 10.1523/JNEUROSCI.10-06-01799.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Zagotta W. N., Aldrich R. W. Voltage-dependent gating of Shaker A-type potassium channels in Drosophila muscle. J Gen Physiol. 1990 Jan;95(1):29–60. doi: 10.1085/jgp.95.1.29. [DOI] [PMC free article] [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