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.
- 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.
- 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.
Université Claude Bernard – Lyon 1
Bât Raphaël Dubois, 2nd floor
43 Boulevard du 11 novembre 1918
- 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).