INTRODUCTION: Myotonia congenita (MC) is caused by congenital defects in the muscle chloride channel CLC-1. This study used muscle velocity recovery cycles (MVRCs) to investigate how membrane function is affected. METHODS: MVRCs and responses to repetitive stimulation were compared between 18 patients with genetically confirmed MC (13 recessive, 7 dominant) and 30 age-matched, normal controls. RESULTS: MC patients exhibited increased early supernormality, but this was prevented by treatment with sodium channel blockers. After multiple conditioning stimuli, late supernormality was enhanced in all MC patients, indicating delayed repolarization. These abnormalities were similar between the MC subtypes, but recessive patients showed a greater drop in amplitude during repetitive stimulation. CONCLUSIONS: MVRCs indicate that chloride conductance only becomes important when muscle fibers are depolarized. The differential responses to repetitive stimulation suggest that, in dominant MC, the affected chloride channels are activated by strong depolarization, consistent with a positive shift of the CLC-1 activation curve.
INTRODUCTION: Myotonia congenita (MC) is caused by congenital defects in the muscle chloride channel CLC-1. This study used muscle velocity recovery cycles (MVRCs) to investigate how membrane function is affected. METHODS: MVRCs and responses to repetitive stimulation were compared between 18 patients with genetically confirmed MC (13 recessive, 7 dominant) and 30 age-matched, normal controls. RESULTS: MC patients exhibited increased early supernormality, but this was prevented by treatment with sodium channel blockers. After multiple conditioning stimuli, late supernormality was enhanced in all MC patients, indicating delayed repolarization. These abnormalities were similar between the MC subtypes, but recessive patients showed a greater drop in amplitude during repetitive stimulation. CONCLUSIONS: MVRCs indicate that chloride conductance only becomes important when muscle fibers are depolarized. The differential responses to repetitive stimulation suggest that, in dominant MC, the affected chloride channels are activated by strong depolarization, consistent with a positive shift of the CLC-1 activation curve.
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: Sara Locci; Rosanna Cardani; Paola Brunori; Sabrina Lucchiari; Giacomo P Comi; Antonio Federico; Nicola De Stefano; Giovanni Meola; Andrea Mignarri Journal: Neurol Sci Date: 2021-08-13 Impact factor: 3.307
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