ADP-ribose stimulates the calcium release channel RyR1 in skeletal muscle of rat.
The Ca(2+) mobilizing metabolite cyclic ADP-ribose has been shown to release Ca(2+) from intracellular ryanodine sensitive stores in many cells. However, the activation of the ryanodine receptor of skeletal muscle by cADP-ribose (cADPr) and its precursor and metabolite (beta-NAD(+) and ADPr) remains to be discussed. We studied the effect of ADPr on the Ca(2+) release channel of skeletal muscle RyR1 after incorporation of microsomes isolated from fast muscles of rat in planar lipid bilayers. We observed an increase in the electrophysiological activity of the channel after addition of ADPr (10 microM) at micromolar Ca(2+) concentrations, characterized by a time-lag. The increase in P(o) is mainly due to an increase in the open frequency. The long time course observed for the development of the ADPr effect may indicate that this activation induces a change in the conformation of the RyR1 channel, which increases its sensitivity to calcium.
Bastide
B
B
Laboratoire de Plasticité Neuromusculaire, Université des Sciences et Technologies de Lille, Bât. SN4, IFR 118, 59655, Villeneuve d'Ascq Cedex, France. Bruno.Bastide@univ.lille.fr
Snoeckx
K
K
Mounier
Y
Y
D000246:Adenosine Diphosphate Ribose / Q000494:pharmacology*; D000818:Animals; D004553:Electric Conductivity; D007700:Kinetics; D018482:Muscle, Skeletal / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D019837:Ryanodine Receptor Calcium Release Channel / Q000502:physiology*
D019837:Ryanodine Receptor Calcium Release Channel; D000246:Adenosine Diphosphate Ribose