Open AccessAbsence of the β subunit ( cchb1 ) of the skeletal muscle dihydropyridine receptor alters expression of the α 1 subunit and eliminates excitation-contraction coupling
Author(s) -
Ronald G. Gregg,
Albee Messing,
Caroline Strube,
Maryline Beurg,
Richard L. Moss,
Mary Behan,
Manana Sukhareva,
Susan R. Haynes,
Jeanne A. Powell,
Roberto Coronado,
Patricia A. Powers
Publication year - 1996
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.93.24.13961
Subject(s) - ryanodine receptor , endoplasmic reticulum , myogenesis , skeletal muscle , protein subunit , biology , interleukin 10 receptor, alpha subunit , dihydropyridine , medicine , biophysics , endocrinology , g alpha subunit , chemistry , microbiology and biotechnology , biochemistry , calcium , gene
The multisubunit (alpha 1s, alpha 2/delta, beta 1, and gamma) skeletal muscle dihydropyridine receptor transduces transverse tubule membrane depolarization into release of Ca2+ from the sarcoplasmic reticulum, and also acts as an L-type Ca2+ channel. The alpha 1s subunit contains the voltage sensor and channel pore, the kinetics of which are modified by the other subunits. To determine the role of the beta 1 subunit in channel activity and excitation-contraction coupling we have used gene targeting to inactivate the beta 1 gene. beta 1-null mice die at birth from asphyxia. Electrical stimulation of beta 1-null muscle fails to induce twitches, however, contractures are induced by caffeine. In isolated beta 1-null myotubes, action potentials are normal, but fail to elicit a Ca2+ transient. L-type Ca2+ current is decreased 10- to 20-fold in the beta 1-null cells compared with littermate controls. Immunohistochemistry of cultured myotubes shows that not only is the beta 1 subunit absent, but the amount of alpha 1s in the membrane also is undetectable. In contrast, the beta 1 subunit is localized appropriately in dysgenic, mdg/mdg, (alpha 1s-null) cells. Therefore, the beta 1 subunit may not only play an important role in the transport/insertion of the alpha 1s subunit into the membrane, but may be vital for the targeting of the muscle dihydropyridine receptor complex to the transverse tubule/sarcoplasmic reticulum junction.