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 voltage-gated CAV1.1 Ca2++ channel (also called dihydropyridine receptor, DHPR). This in turns gates open the Ca2++ release channel (type 1 ryanodine receptor, RYR1) in the adjacent sarcoplasmic reticulum (SR) membrane, through direct protein-protein interactions. As a consequence, Ca2++ 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. We have a specific interest for these mechanisms which play a key role in muscle function and we devote particular efforts to assess their operating function in real-time, in intact isolated muscle cells. Our research aims at identifying their detailed functional properties and how these are altered in pathological conditions. We currently have three main goals: 1- Understand basic mechanisms of Ca2++ entry through the muscle cell membrane with an explicit interest for the role of the voltage-gated Ca2++ entry through the DHPR. 2- Demonstrate how the physiological function of the DHPR and of RYR1 is altered by specific disease mutations of their encoding genes. 3- Define how phosphoinositides (PtdInsPs) are involved in the control of intracellular Ca2++ and determine whether this plays a role in muscle dysfunctions due to deficient PtdInsPs metabolism.
- Andersen's syndrome mutants produce a knockdown of inwardly rectifying K+ channel in mouse skeletal muscle in vivo.
Simkin D, Robin G, Giuliano S, Vukolic A, Moceri P, Guy N, Wagner KD, Lacampagne A, Allard B, Bendahhou S. Cell Tissue Res. (2018) 371:309-323.
- 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(50):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.
- Osmosensation in TRPV2 dominant negative expressing skeletal muscle fibres.
Zanou N, Mondin L, Fuster C, Seghers F, Dufour I, de Clippele M, Schakman O, Tajeddine N, Iwata Y, Wakabayashi S, Voets T, Allard B, Gailly P. J Physiol. (2015) 593:3849-3863.
- Phosphoinositides in Ca2+ signaling and excitation-contraction coupling in skeletal muscle: an old player and newcomers.
Csernoch L, Jacquemond V. J Muscle Res Cell Motil. (2015) 36:491-499.
- 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, 315-30.
- Phosphoinositide substrates of myotubularin affect voltage-activated Ca2+ release in skeletal muscle
González Rodríguez E, Lefebvre R, Bodnár D, Legrand C, Szentesi P, Vincze J, Poulard K, Bertrand-Michel J, Csernoch L, Buj-Bello A, Jacquemond V Pflugers Arch (2014) 466, 937-985.
- Major contribution of sarcoplasmic reticulum Ca2+ depletion during long-lasting activation of skeletal muscle
Robin G, Allard B J Gen Physiol (2013) 141, 557-565.
- Dihydropyridine receptors actively control gating of ryanodine receptors in resting mouse skeletal muscle fibres
Robin G, Allard B J Physiol (2012) 590, 6027-6036.
- Sarcoplasmic reticulum Ca2+ permeation explored from the lumen side in mdx muscle fibers under voltage control
Robin G, Berthier C, Allard B J Gen Physiol (2012) 139, 209-218.
- Defects in Ca2+ release associated with local expression of pathological ryanodine receptors in mouse muscle fibres
Lefebvre R, Legrand C, González-Rodríguez E, Groom L, Dirksen RT, Jacquemond V J Physiol (2011) 589, 5361-5382.
- Caveolin-3 is a direct molecular partner of the Cav1 1 subunit of the skeletal muscle L-type calcium channel
Couchoux H, Bichraoui H, Chouabe C, Altafaj X, Bonvallet R, Allard B, Ronjat M, Berthier C Int J Biochem Cell Biol (2011) 43, 713-720.
- Altered myoplasmic Ca2+ handling in rat fast-twitch skeletal muscle fibres during disuse atrophy
Weiss N, Andrianjafiniony T, Dupré-Aucouturier S, Pouvreau S, Desplanches D,Jacquemond V Pflugers Arch (2010) 459, 631-644.
- In vivo expression of G-protein β1γ2 dimer in adult mouse skeletal muscle alters L-type calcium current and excitation-contraction coupling
Weiss N, Legrand C, Pouvreau S, Bichraoui H, Allard B, Zamponi GW, De Waard M, Jacquemond V J Physiol (2010) 588, 2945-2960.
- Transient receptor potential canonical type 1 (TRPC1) operates as a sarcoplasmic reticulum calcium leak channel in skeletal muscle
Berbey C, Weiss N, Legrand C, Allard B J Biol Chem (2009) 284, 36387-36394.
- Electrically silent divalent cation entries in resting and active voltage-controlled muscle fibers
Berbey C, Allard B Biophys J (2009) 96, 2648-2657.
- The L-type voltage-dependent Ca2+ channel EGL-19 controls body wall muscle function in Caenorhabditis elegans
Jospin M, Jacquemond V, Mariol MC, Ségalat L, Allard B J Cell Biol (2002) 159, 337-348.
- Elevated subsarcolemmal Ca2+ in mdx mouse skeletal muscle fibers detected with Ca2+-activated K+ channels
Mallouk N, Jacquemond V, Allard B Proc Natl Acad Sci USA (2000) 97, 4950-4955.
- Activation of Ca2+-activated K+ channels by an increase in intracellular Ca2+ induced by depolarization of mouse skeletal muscle fibres.
Jacquemond V, Allard B J Physiol (1998) 509, 93-102.
- AFM-Téléthon (2015-2016): Phosphoinositides and Ca2+ signaling in normal and diseased skeletal muscle (coordinator).
- AFM-Téléthon (2013-2016): The sodium channel Nav1.4 at the neuromuscular junction: role in congenital mysathenic syndromes (partner).
- AFM-Téléthon (2015-2017): Physiopathology of voltage-activated Ca2+ influx in normal and diseased skeletal muscle (coordinator).