S Veronica Tan1,2,3, Werner J Z'Graggen4, Michael G Hanna1,2, Hugh Bostock1,2,4. 1. MRC Centre for Neuromuscular Diseases, UCL Institute of Neurology, The National Hospital for Neurology and Neurosurgery, Queen Square, London, WC1N 3BG, United Kingdom. 2. Institute of Neurology, University College London, Queen Square, London, United Kingdom. 3. Department of Neurology and Neurophysiology, St Thomas' Hospital, Guy's and St Thomas' NHS Foundation Trust and Department of Academic Neurosciences, Kings College London, United Kingdom. 4. Departments of Neurosurgery and Neurology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
Abstract
INTRODUCTION: The gain-of-function mutations that underlie sodium channel myotonia (SCM) and paramyotonia congenital (PMC) produce differing clinical phenotypes. We used muscle velocity recovery cycles (MVRCs) to investigate membrane properties. METHODS: MVRCs and responses to trains of stimuli were compared in patients with SCM (n = 9), PMC (n = 8), and normal controls (n = 26). RESULTS: The muscle relative refractory period was reduced in SCM, consistent with faster recovery of the mutant sodium channels from inactivation. Both SCM and PMC showed an increased early supernormality and increased mean supernormality following multiple conditioning stimuli, consistent with slowed sodium channel inactivation. Trains of fast impulses caused a loss of amplitude in PMC, after which only half of the muscle fibers recovered, suggesting that the remainder stayed depolarized by persistent sodium currents. DISCUSSION: The differing effects of mutations on sodium channel function can be demonstrated in human subjects in vivo using this technique. Muscle Nerve 57: 586-594, 2018.
INTRODUCTION: The gain-of-function mutations that underlie sodium channel myotonia (SCM) and paramyotonia congenital (PMC) produce differing clinical phenotypes. We used muscle velocity recovery cycles (MVRCs) to investigate membrane properties. METHODS: MVRCs and responses to trains of stimuli were compared in patients with SCM (n = 9), PMC (n = 8), and normal controls (n = 26). RESULTS: The muscle relative refractory period was reduced in SCM, consistent with faster recovery of the mutant sodium channels from inactivation. Both SCM and PMC showed an increased early supernormality and increased mean supernormality following multiple conditioning stimuli, consistent with slowed sodium channel inactivation. Trains of fast impulses caused a loss of amplitude in PMC, after which only half of the muscle fibers recovered, suggesting that the remainder stayed depolarized by persistent sodium currents. DISCUSSION: The differing effects of mutations on sodium channel function can be demonstrated in human subjects in vivo using this technique. Muscle Nerve 57: 586-594, 2018.
Authors: N Mitrović; A L George; R Heine; S Wagner; U Pika; U Hartlaub; M Zhou; H Lerche; C Fahlke; F Lehmann-Horn Journal: J Physiol Date: 1994-08-01 Impact factor: 5.182
Authors: S Veronica Tan; Werner J Z'graggen; Delphine Boërio; Dipa L Raja Rayan; Robin Howard; Michael G Hanna; Hugh Bostock Journal: Muscle Nerve Date: 2012-08 Impact factor: 3.217
Authors: S Veronica Tan; Werner J Z'graggen; Delphine Boërio; Christopher Turner; Michael G Hanna; Hugh Bostock Journal: Muscle Nerve Date: 2016-05-24 Impact factor: 3.217
Authors: Michael G Thor; Vinojini Vivekanandam; Marisol Sampedro-Castañeda; S Veronica Tan; Karen Suetterlin; Richa Sud; Siobhan Durran; Stephanie Schorge; Dimitri M Kullmann; Michael G Hanna; Emma Matthews; Roope Männikkö Journal: Sci Rep Date: 2019-11-26 Impact factor: 4.379
Authors: Karen J Suetterlin; S Veronica Tan; Roope Mannikko; Rahul Phadke; Michael Orford; Simon Eaton; Avan A Sayer; Miranda D Grounds; Emma Matthews; Linda Greensmith; Michael G Hanna Journal: JCSM Rapid Commun Date: 2021-05-05