Letter | Published:

Normalization of current kinetics by interaction between the α1and β subunits of the skeletal muscle dihydropyridine-sensitive Ca2+ channel

Naturevolume 352pages527530 (1991) | Download Citation

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Abstract

PURIFICATION of skeletal muscle dihydropyridine binding sites has enabled protein complexes to be isolated from which Ca2+ currents have been reconstituted. Complementary DNAs encoding the five subunits of the dihydropyridine receptor, α1, β, γ, α2 and δ (ref. 1), have been cloned2–6 and it is now recognized that α2 and δ are derived from a common precursor7,8. The α1, subunit can itself produce Ca2+ currents, as was demonstrated using mouse L cells lacking α2δ (refs 9,10), β (ref. 10) and γ (our unpublished results). In L cells, stable expression of skeletal muscle α1 alone was sufficient to generate voltage-sensitive, high-threshold L-type Ca2+ channel currents which were dihydropyridine-sensitive and blocked by Cd2+, but the activation kinetics were about 100 times slower than expected for skeletal muscle Ca2+ channel currents. This could have been due to the cell type in which α1 , was being expressed or to the lack of a regulatory component particularly one of the subunits that copurifies with α1. We show here that coexpression of skeletal muscle β with skeletal muscle α1, generates cell lines expressing Ca2+ channel currents with normal activation kinetics as evidence for the participation of the dihydropyridine-receptor β subunits in the generation of skeletal muscle Ca2+ channel currents.

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Author information

Author notes

    • Peter Ruth
    •  & Franz Hofmann

    Present address: Institute of Pharmacology, Technical University of Munich, D-8000, Munich, Germany

Affiliations

  1. Department of Molecular Physiology & Biophysics, Baylor College of Medicine, Houston, Texas, 77030, USA

    • Antonio E. Lacerda
    • , Edward Perez-Reyes
    • , Lutz Birnbaumer
    •  & Arthur M. Brown
  2. Department of Cell Biology, Baylor College of Medicine, Houston, Texas, 77030, USA

    • Haeyoung S. Kim
    •  & Lutz Birnbaumer
  3. Department of Division of Neuroscience, Baylor College of Medicine, Houston, Texas, 77030, USA

    • Lutz Birnbaumer
  4. Institute of Physiological Chemistry, Faculty of Medicine, University of Saarland, D-6650, Homburg/Saar, Saarland, Germany

    • Peter Ruth
    • , Veit Flockerzi
    •  & Franz Hofmann

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https://doi.org/10.1038/352527a0

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