Our research is focused on the physiology and pathophysiology of skeletal muscle function. It aims at understanding how specific mechanisms involved in the control of skeletal muscle Ca2+ homeostasis and excitation-contraction (EC) coupling operate under normal and disease conditions. Muscle contraction is initiated when action potentials fired at the end-plate of the muscle cells propagate throughout the plasma membrane and trigger a conformational change of the CaV1.1 protein which gates open a Ca2+ release channel (type 1 ryanodine receptor, RyR1) in the sarcoplasmic reticulum (SR) membrane. Ca2+ then gets released from the SR into the cytosol and triggers contraction. Besides Ca2+ release from the SR there is also Ca2+ entry from the extracellular medium.
Our main current projects aim at:
1- Understanding basic mechanisms involved in the regulation of CaV1.1 and of RyR1 function.
2- Demonstrating how excitability and/or EC coupling are altered by specific disease mutations affecting the genes encoding CaV1.1, RyR1 and also other proteins involved in the function and/or maintenance of the EC coupling machinery.
The overall project stands on a set of methods and expertise that includes molecular biology and biochemistry, in vivo gene transfer and a state of the art combination of electrophysiology and fluorescence detection on single isolated differentiated muscle cells from mouse.
- When muscle Ca2+ channels carry monovalent cations through gating pores: insights into the pathophysiology of type 1 hypokalaemic periodic paralysis.
Allard B, Fuster C. J Physiol (2018) in press.
- Na leak with gating pore properties in hypokalemic periodic paralysis V876E mutant muscle Ca channel.
Fuster C, Perrot J, Berthier C, Jacquemond V, Charnet P, Allard B. J Gen Physiol (2017) 149:1139-1148.
- Impaired excitation-contraction coupling in muscle fibres from the dynamin2R465W mouse model of centronuclear myopathy.
Kutchukian C, Szentesi P, Allard B, Trochet D, Beuvin M, Berthier C, Tourneur Y, Guicheney P, Csernoch L, Bitoun M, Jacquemond V. J Physiol (2017) 595:7369-7382..
- Elevated resting H+ current in the R1239H type 1 hypokalaemic periodic paralysis mutated Ca2+ channel.
Fuster C, Perrot J, Berthier C, Jacquemond V, Allard B. J Physiol (2017) ;595:6417-6428.
- Phosphatidylinositol 3-kinase inhibition restores Ca2+ release defects and prolongs survival in myotubularin-deficient mice.
Kutchukian C, Lo Scrudato M, Tourneur Y, Poulard K, Vignaud A, Berthier C, Allard B, Lawlor MW, Buj-Bello A, Jacquemond V. PNAS (2016) 113:14432-14437.
- Voltage-gated Ca2+ influx through L-type channels contributes to sarcoplasmic reticulum Ca2+ loading in skeletal muscle.
Robin G, Allard B. J Physiol (2015) 593:4781-4797.
- Depression of voltage-activated Ca2+ release in skeletal muscle by activation of a voltage-sensing phosphatase.
Berthier C, Kutchukian C, Bouvard C, Okamura Y, Jacquemond V. J Gen Physiol (2015) 145:315-330.
- Phosphoinositide substrates of myotubularin affect voltage-activated Ca≤? release in skeletal muscle.
RodrÌguez EG, Lefebvre R, Bodn·r D, Legrand C, Szentesi P, Vincze J, Poulard K, Bertrand-Michel J, Csernoch L, Buj-Bello A, Jacquemond V. Pflugers Arch (2014) 466:973-985.
- Dihydropyridine receptors actively control gating of ryanodine receptors in resting mouse skeletal muscle fibres.
Robin G, Allard B. J Physiol (2012) 590:60275-6036.
- Defects in Ca2+ release associated with local expression of pathological ryanodine receptors in mouse muscle fibres.
Lefebvre R, Legrand C, Gonz·lez-RodrÌguez E, Groom L, Dirksen RT, Jacquemond V. J Physiol (2011) 589:5361-5382.
- AFM-Téléthon / MyoNeurALP Alliance (2016-2021)