Nature 354, 301 - 304 (28 November 1991); doi:10.1038/354301a0

Primary structure and functional expression of a developmentally regulated skeletal muscle chloride channel

Klaus Steinmeyer, Christoph Ortland & Thomas J. Jentsch^*

Centre for Molecular Neurobiology (ZMNH), Hamburg University, Martinistrasse 52, D-2000 Hamburg 20,Germany
^*To whom corresspondence should be addressed.

SKELETAL muscle is unusual in that 70–85% of resting membrane conductance is carried by chloride ions¹. This conductance is essential for membrane-potential stability, as its block by 9-anthracene-carboxylic acid and other drugs causes myotonia^2,3. Fish electric organs are developmentally derived from skeletal muscle, suggesting that mammalian muscle may express a homologue of the Torpedo mamorataelectroplax chloride channel^4,5. We have now cloned the complementary DNA encoding a rat skeletal muscle chloride channel by homology screening to the Cl^- channel from Torpedo ⁴ (Fig. la). It encodes a 994-amino-acid protein which is about 54% identical to the Torpedo channel and is predominantly expressed in skeletal muscle. Messenger RNA amounts in that tissue increase steeply in the first 3–4 weeks after birth, in parallel with the increase in muscle Cl^- conductance⁶. Expression from cRNA in Xenopus oocytes leads to 9-anthracene-carboxylic acid-sensitive currents with time and voltage dependence typical for macroscopic muscle Cl^- conductance. This and the functional destruction of this channel in mouse myotonia⁷ suggests that we have cloned the major skeletal muscle chloride channel.

References

1.	Bretag, A. H. Physiol. Rev. 67, 618−724 (1987). | PubMed | ChemPort |
2.	Rüdel, R. & Lehmann-Horn, F. Physiol. Rev. 65, 310−356 (1985). | PubMed | ISI | ChemPort |
3.	Bryant, S. H. & Morales-Aguilera, A. J. Physiol., Lond. 219, 367−383 (1971). | PubMed | ISI | ChemPort |
4.	Jentsch, T. J., Steinmeyer, K. & Schwarz, G. Nature 348, 510−514 (1990). | Article | PubMed | ISI | ChemPort |
5.	Miller, C. & Richard, E. A. in Chloride Channels and Carriers in Nerve, Muscle, and Glial Cells (eds Alvarez-Leefsmans, F. J. & Russel, J. M.) 383−405 (Plenum, New York, 1990).
6.	Conte Camerino, D., De Luca, A., Mambrini, M. & Vrbovà, G. Pflügers Arch. 413, 568−570 (1989). | Article | ChemPort |
7.	Steinmeyer, K. et al. Nature 354, 304−308 (1991). | Article | PubMed | ISI | ChemPort |
8.	Kyte, J. & Doolittle, R. F. J. molec. Biol. 157, 105−132 (1982). | Article | PubMed | ISI | ChemPort |
9.	Kimes, B. W. & Brandt, B. L. Expl Cell Res. 98, 349−366 (1976). | ChemPort |
10.	Cooperman, S. S. et al. Proc. natn. Acad. Sci. U.S.A. 84, 8721−8725 (1987). | ChemPort |
11.	Trimmer, J. S. et al. Neuron 3, 33−49 (1989). | Article | PubMed | ISI | ChemPort |
12.	Trimmer, J. S., Cooperman, S. S., Agnew, W. S. & Mandel, G. Devl Biol. 142, 360−367 (1990). | ChemPort |
13.	Kallen, R. L. et al. Neuron 4, 233−242 (1990). | Article | PubMed | ISI | ChemPort |
14.	Mishina, M. et al. Nature 321, 406−411 (1986). | Article | PubMed | ISI | ChemPort |
15.	Witzemann, V., Barg, B., Criado, M., Stein, E. & Sakmann, B. FEBS Lett. 242, 419−424 (1989). | Article | PubMed | ChemPort |
16.	Palade, P. T. & Barchi, R. L. J. gen. Physiol. 69, 325−342 (1977). | Article | PubMed | ISI | ChemPort |
17.	Miller, C. Phil. Trans. R. Soc. B 299, 401−411 (1982). | ISI | ChemPort |
18.	Miller, C. & White, M. M. Proc. natn. Acad. Sci. U.S.A. 81, 2772−2775 (1984). | ChemPort |
19.	Bauer, C. K., Steinmeyer, K., Schwarz, J. R. & Jentsch, T. J. Proc. natn. Acad. Sci. U.S.A. (in the press).
20.	Blatz, A. L. & Magleby, K. L. Biophys. J. 43, 237−241 (1983). | PubMed | ISI | ChemPort |
21.	Blatz, A. L. & Magleby, K. L. Biophys. J. 47, 119−123 (1985). | PubMed | ISI | ChemPort |
22.	Kozak, M. Nucleic Acids Res. 12, 857−872 (1984). | PubMed | ISI | ChemPort |
23.	Colman, A. in Transcription and Translation (eds Hames, B. D. & Higgins, S. J.) 271−302 (IRL, Oxford, 1984). | ChemPort |
24.	Higuchi, R. in PCR Technology (ed. Erlich, H. A.) 61−70 (Stockton, New York, 1989).