Absence of the beta subunit (cchb1) of the skeletal muscle dihydropyridine receptor alters expression of the alpha 1 subunit and eliminates excitation-contraction coupling

Proc Natl Acad Sci U S A. 1996 Nov 26;93(24):13961-6. doi: 10.1073/pnas.93.24.13961.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Action Potentials / physiology
  • Animals
  • Calcium / metabolism*
  • Calcium Channels / biosynthesis*
  • Calcium Channels / genetics*
  • Calcium Channels / physiology
  • Calcium Channels, L-Type
  • Cloning, Molecular
  • Embryo, Mammalian
  • Genomic Library
  • Macromolecular Substances
  • Mice
  • Mice, Knockout
  • Muscle Contraction*
  • Muscle, Skeletal / physiology*
  • Myofibrils / physiology
  • Myofibrils / ultrastructure
  • Recombinant Proteins / biosynthesis
  • Sarcoplasmic Reticulum / metabolism


  • Calcium Channels
  • Calcium Channels, L-Type
  • Macromolecular Substances
  • Recombinant Proteins
  • Calcium