Transient loss of voltage control of Ca2+ release in the presence of maurocalcine in skeletal muscle.
In skeletal muscle, sarcoplasmic reticulum (SR) calcium release is controlled by the plasma membrane voltage through interactions between the voltage-sensing dihydropyridine receptor (DHPr) and the ryanodine receptor (RYr) calcium release channel. Maurocalcine (MCa), a scorpion toxin peptide presenting some homology with a segment of a cytoplasmic loop of the DHPr, has been previously shown to strongly affect the activity of the isolated RYr. We injected MCa into mouse skeletal muscle fibers and measured intracellular calcium under voltage-clamp conditions. Voltage-activated calcium transients exhibited similar properties in control and in MCa-injected fibers during the depolarizing pulses, and the voltage dependence of calcium release was similar under the two conditions. However, MCa was responsible for a pronounced sustained phase of Ca(2+) elevation that proceeded for seconds following membrane repolarization, with no concurrent alteration of the membrane current. The magnitude of the underlying uncontrolled extra phase of Ca(2+) release correlated well with the peak calcium release during the pulse. Results suggest that MCa binds to RYr that open on membrane depolarization and that this interaction specifically alters the process of repolarization-induced closure of the channels.
Pouvreau
Sandrine
S
Physiologie Intégrative Cellulaire et Moléculaire, Université Claude Bernard Lyon 1, UMR CNRS 5123, Bâtiment Raphael Dubois, 43 boulevard du 11 novembre 1918, F 69622 Villeurbanne Cedex, France.
Csernoch
Laszlo
L
Allard
Bruno
B
Sabatier
Jean Marc
JM
De Waard
Michel
M
Ronjat
Michel
M
Jacquemond
Vincent
V
D000818:Animals; D002118:Calcium / Q000502:physiology*; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D015640:Ion Channel Gating; D008564:Membrane Potentials; D051379:Mice; D009119:Muscle Contraction; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000502:physiology*; D018482:Muscle, Skeletal / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D019837:Ryanodine Receptor Calcium Release Channel / Q000502:physiology; D012519:Sarcoplasmic Reticulum / Q000502:physiology; D012604:Scorpion Venoms / Q000494:pharmacology*
D019837:Ryanodine Receptor Calcium Release Channel; D012604:Scorpion Venoms; C406406:maurocalcine; D002118:Calcium