In vivo expression of G-protein beta1gamma2 dimer in adult mouse skeletal muscle alters L-type calcium current and excitation-contraction coupling.
A number of G-protein-coupled receptors are expressed in skeletal muscle but their roles in muscle physiology and downstream effector systems remain poorly investigated. Here we explored the functional importance of the G-protein betagamma (Gbetagamma) signalling pathway on voltage-controlled Ca(2+) homeostasis in single isolated adult skeletal muscle fibres. A GFP-tagged Gbeta(1)gamma(2) dimer was expressed in vivo in mice muscle fibres. The GFP fluorescence pattern was consistent with a Gbeta(1)gamma(2) dimer localization in the transverse-tubule membrane. Membrane current and indo-1 fluorescence measurements performed under voltage-clamp conditions reveal a drastic reduction of both L-type Ca(2+) current density and of peak amplitude of the voltage-activated Ca(2+) transient in Gbeta(1)gamma(2)-expressing fibres. These effects were not observed upon expression of Gbeta(2)gamma(2), Gbeta(3)gamma(2) or Gbeta(4)gamma(2). Our data suggest that the G-protein beta(1)gamma(2) dimer may play an important regulatory role in skeletal muscle excitation-contraction coupling.
Weiss
Norbert
N
Université Lyon 1, UMR CNRS 5123, Physiologie Intégrative Cellulaire et Moléculaire, Bâtiment R. Dubois, 43 boulevard du 11 novembre 1918, Villeurbanne, France. norbert.weiss@yahoo.fr
Legrand
Claude
C
Pouvreau
Sandrine
S
Bichraoui
Hicham
H
Allard
Bruno
B
Zamponi
Gerald W
GW
De Waard
Michel
M
Jacquemond
Vincent
V
D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000502:physiology*; D002478:Cells, Cultured; D019281:Dimerization; D044387:GTP-Binding Protein beta Subunits / Q000378:metabolism*; D015870:Gene Expression / Q000502:physiology; D015640:Ion Channel Gating / Q000502:physiology*; D051379:Mice; D009119:Muscle Contraction / Q000502:physiology*; D018485:Muscle Fibers, Skeletal / Q000502:physiology*
D020746:Calcium Channels, L-Type; D044387:GTP-Binding Protein beta Subunits; D002118:Calcium