Launikonis Group - Muscle research

Lab group

The main interest of the lab is Excitation-Contraction Coupling and Calcium Regulation in Skeletal Muscle. The focus is to understand the mechanisms that (i) control calcium release during activity in muscle, and (ii) maintain calcium homeostasis in skeletal muscle fibres. Within this broad focus, the roles of ion channels, pumps and membrane lipid composition in skeletal muscle physiology are studied. Significant emphasis is given to how properties of the muscle change in disease and other stressed states. To unravel the physiological mechanisms that control skeletal muscle activity, imaging of muscle cell structures and calcium movements are performed.

We have recently started working human muscle fibres obtained from needle biopsies, in conjunction with our colleagues in The School of Human Movement. We hope to gain a greater understand of ionic regulation in human muscle health, exercise and disease states.

Group Head

Staff

Students

  • 2022-2025: Australian Research Council Discovery Project, $608,000, Regulated muscle-based thermogenesis for body temperature regulation.
  • 2020-2023: Australian Research Council Discovery Project, A$508,000: Sarcoplasmic reticulum-mitochondrial functional interactions in muscle.
  • 2020-2022: RYR1 Foundation, Research Grant, US$100,000: Assessment of the ability of small molecule RyR modulators to correct the Ca2+ fluxes in skeletal muscle fibers with RyR myopathy.
  • 2020-2022: ​Perry M, Gilles R, Bjorksten A, Launikonis BS, Diagnosing Malignant Hyperthermia from Muscle Fibres obtained from Needle Biopsy, Australia and New Zealand College of Anesthetists,  AUD$60,000
  • 2019-2021: AFM-Telethon, Research Grant, A$122,000: Junctional membrane calcium dynamics in skeletal muscle fibres with ryanodine receptor variants.
  • 2019-2020: Jain Foundation, Research Grant, A$202,000: Ca2+ handling and tubular (t-) system function in dysferlinopathy.
  • 2018-2021: Australian Research Council Discovery Project, A$530,000: Calcium cycling and heat generation in skeletal muscle fibres.

 

 

Meizoso-Huesca A, Pearce L, Barclay CJ, Launikonis BS (2022). Ca2+ leak through ryanodine receptor 1 regulates thermogenesis in resting skeletal muscle. Proc Natl Acad Sci U S A. 119(4):e2119203119.

Seng C, Pearce L, Meizoso-Huesca A, Singh DP, Murphy RM, Lamboley CR, Launikonis BS (2022). Tiny changes in cytoplasmic [Ca2+] cause large changes in mitochondrial Ca2+: what are the triggers and functional implications? Am J Physiol Cell Physiol. 323(4):C1285-C1289.

Barclay CJ, Launikonis BS (2022). A mathematical model to quantify RYR Ca2+ leak and associated heat production in resting human skeletal muscle fibers. J Gen Physiol. 154(9):e202112994. doi: 10.1085/jgp.202112994.

Pearce L, Meizoso-Huesca A, Seng C, Lamboley CR, Singh DP, Launikonis BS (2022). Ryanodine receptor activity and store-operated Ca2+ entry: Critical regulators of Ca2+ content and function in skeletal muscle. J Physiol. doi: 10.1113/JP279512. 

Lamboley CR, Pearce L, Seng C, Meizoso-Huesca A, Singh DP, Frankish BP, Kaura V, Lo HP, Ferguson C, Allen PD, Hopkins PM, Parton RG, Murphy RM, van der Poel C, Barclay CJ, Launikonis BS (2021). Ryanodine receptor leak triggers fibre Ca2+ redistribution to preserve force and elevate basal metabolism in skeletal muscleScience Advances 7, eabi7166.

Meizoso-Huesca A, Launikonis BS (2021). The Orai1 inhibitor BTP2 has multiple effects on Ca2+ handling in skeletal muscle. J Gen Physiol 153, e202012747.

Rebbeck RT, Singh DP, Janicek KA, Bers DM, Thomas DD, Launikonis BS & Cornea RL(2020). RyR1-targeted drug discovery pipeline integrating FRET-based high-throughput screening and human myofiber dynamic Ca2+ assays. Sci Rep 10(1):1791.

Barclay CJ & Launikonis BS (2019). Components of heat activation in skeletal muscle. J Muscle Res Cell Mot doi: 10.1007/s10974-019-09547-5.

Koenig X, Choi RH, Schicker K, Singh DP, Hilber K & Launikonis BS (2019). Mechanistic insights into store-operated Ca2+ entry during excitation-contraction coupling in skeletal muscle. BBA - Molecular Cell Research 1866, 1239-1248. (Special Issue: European Calcium Society Meeting).

Cully TR, Choi RH, Bjorksten AR, Stephenson DG, Murphy RM & Launikonis BS (2018). Junctional membrane Ca2+-dynamics in human muscle fibers are altered by malignant hyperthermia causative RyR mutation. Proc Natl Acad Sci USA. 115, 8215-8220.

Koenig X, Choi RH & Launikonis BS (2018). Store-operated Ca2+ entry is activated by every action potential in skeletal muscle. Communications Biology 1, 31.

Launikonis BS, Cully TR, Csernoch L & Stephenson DG (2018). NHE- and diffusion-dependent proton fluxes across the tubular system membranes of fast-twitch muscle fibers of the rat. J Gen Physiol 150, 95-110.

Choi RH, Koenig X & Launikonis BS (2017). Dantrolene requires Mg2+ to arrest malignant hyperthermia. Proc Natl Acad Sci USA 114, 4811-4815.

Bakker AJ, Cully TR, Wingate C, Barclay CJ & Launikonis BS (2017). Doublet stimulation increases Ca2+ binding to troponin C to ensure rapid force development in skeletal muscle. J Gen Physiol 149, 323-334.

Cully TR, Murphy RM, Roberts L, Raastad T, Fassett RG, Coombes JS, Jayasinghe ID & Launikonis BS (2017). Human skeletal muscle plasmalemma alters its structure to change its Ca2+-handling following heavy-load resistance exercise. Nat Commun 8, 14266. 

Cully, Tanya R.Edwards, Joshua N.Murphy, Robyn M. and Launikonis, Bradley S. (2016) A quantitative description of tubular system Ca2+ handling in fast- and slow-twitch muscle fibresJournal of Physiology594 11: 2795-2810. doi:10.1113/JP271658

Cully, Tanya R. and Launikonis, Bradley S. (2016) Leaky ryanodine receptors delay the activation of store overload-induced Ca2+ release, a mechanism underlying malignant hyperthermia-like events in dystrophic muscleAmerican Journal of Physiology: Cell Physiology310 8: C673-C680. doi:10.1152/ajpcell.00366.2015

Cully, Tanya R.Edwards, Joshua N. and Launikonis, Bradley S. (2014) Activation and propagation of Ca2+ release from inside the sarcoplasmic reticulum network of mammalian skeletal muscleJournal of Physiology592 17: 3727-3746. doi:10.1113/jphysiol.2014.274274

Jayasinghe, Isuru D.Munro, MichelleBaddeley, DavidLaunikonis, Bradley S. and Soeller, Christian (2014) Observation of the molecular organization of calcium release sites in fast- and slowtwitch skeletal muscle with nanoscale imagingJournal of the Royal Society Interface11 99: . doi:10.1098/rsif.2014.0570

Jayasinghe, Isuru D. and Launikonis, Bradley S. (2013) Three-dimensional reconstruction and analysis of the tubular system of vertebrate skeletal muscleJournal of Cell Science126 17: 4048-4058. doi:10.1242/jcs.131565

Jayasinghe, Isuru D.Lo, Harriet P.Morgan, Garry P.Baddeley, DavidParton, Robert G.Soeller, Christian and Launikonis, Bradley S. (2013) Examination of the subsarcolemmal tubular system of mammalian skeletal muscle fibersBiophysical Journal104 11: L19-L21. doi:10.1016/j.bpj.2013.04.029

Cully, Tanya R. and Launikonis, Bradley S. (2013) Store-operated Ca2+ entry is not required for store refilling in skeletal muscleClinical and Experimental Pharmacology and Physiology40 5: 338-344. doi:10.1111/1440-1681.12078

Cully, Tanya R.Edwards, Joshua N.Friedrich, OliverStephenson, D. GeorgeMurphy, Robyn M. and Launikonis, Bradley S. (2012) Changes in plasma membrane Ca-ATPase and stromal interacting molecule 1 expression levels for Ca2+ signaling in dystrophic mdx mouse muscle.American Journal of Physiology - Cell Physiology303 5: C567-C576. doi:10.1152/ajpcell.00144.2012

Edwards, Joshua N.Cully, Tanya R.Shannon, Thomas R.Stephenson, D. George and Launikonis, Bradley S. (2012) Longitudinal and transversal propagation of excitation along the tubular system of rat fast-twitch muscle fibres studied by high speed confocal microscopyJournal of Physiology590 3: 475-491. doi:10.1113/jphysiol.2011.221796

Edwards, Joshua N.Blackmore, Daniel G.Gilbert, Daniel F.Murphy, Robyn M. and Launikonis, Bradley S. (2011) Store-operated calcium entry remains fully functional in aged mouse skeletal muscle despite a decline in STIM1 protein expressionAging Cell10 4: 675-685. doi:10.1111/j.1474-9726.2011.00706.x

Launikonis, Bradley S.Murphy, Robyn M. and Edwards, Joshua N. (2010) Toward the roles of store-operated Ca(2+) entry in skeletal musclePflugers Archiv - European Journal of Physiology460 5: 813-823. doi:10.1007/s00424-010-0856-7

Edwards, Joshua N.Friedrich, OliverCully, Tanya R.von Wegner, FredericMurphy, Robyn M. and Launikonis, Bradley S. (2010) Upregulation of store-operated Ca2+ entry in dystrophic mdx mouse muscleAmerican Journal of Physiology: Cell Physiology299 1: C42-C50. doi:10.1152/ajpcell.00524.2009

Edwards, Joshua N.Murphy, Robyn M.Cully, Tanya R.von Wegner, FredericFriedrich, Oliver and Launikonis, Bradley S. (2010) Ultra-rapid activation and deactivation of store-operated Ca2+ entry in skeletal muscleCell Calcium47 5: 458-467. doi:10.1016/j.ceca.2010.04.001

Launikonis, Bradley S.Stephenson, D. George and Friedrich, Oliver (2009) Rapid Ca2+ flux through the transverse tubular membrane, activated by individual action potentials in mammalian skeletal muscleJournal of Physiology587 10: 2299-2312. doi:10.1113/jphysiol.2009.168682

Edwards, Joshua N. and Launikonis, Bradley S. (2008) The accessibility and interconnectivity of the tubular system network in toad skeletal muscleThe Jounal of Physiology586 21: 5077-5089. doi:10.1113/jphysiol.2008.155127

Launikonis, BS and Rios, E (2007) Store-operated Ca2+ entry during intracellular Ca2+ release in mammalian skeletal muscleJournal of Physiology-london583 1: 81-97. doi:10.1113/jphysiol.2007.135046

Launikonis, B. S.Zhou, J. S.Royer, L.Shannon, T. R.Brum, G. and Rios, E. (2006) Depletion "skraps" and dynamic buffering inside the cellular calcium storeProceedings of The National Academy of Sciences of The United States of America103 8: 2982-2987. doi:10.1073/pnas.0511252103

Effects of inflammation due to COVID-19 infection on cardiac and skeletal muscle

COVID-19 infection induces inflammation that affects the normal function of cardiac and skeletal muscle. To be able to test pharmacological agents against the effects of inflammation it is important that we explore the mechanisms of decline in cardiac and skeletal muscle function under COVID-19 infection.

Effects of exercise on Ca2+ handling and metabolism in human skeletal muscle

Following exercise or training, the adaptations such as increased endurance rely on the change in mitochondrial capacity. The biogenesis of mitochondria is likely triggered by changes in the way Ca2+ is distributed in the post-exercised muscle. This project will use the latest techniques to explore the effects of exercise on human muscle fibres obtained from fresh biopsies.

The evolution of thermogenesis in skeletal muscle

Amphibians and mammals use the same proteins and ultrastrual arrangement of the muscle fibre for contration. However, mammals have evolve to use their muscle for the additional purpose of generating heat to maintain body temperature. It is not clear how this has been possible. This project will employ measure of heat and Ca2+ movements in toads, mice and human muscle to explore the evolution of muscle-based thermogenesis.

If you would like to make a tax deductible donation to muscle research, please contact med.advancement@uq.edu.au. Thank you for your support.

Find out more about our research environment and how to apply to do a short or long-term research project with us.