[pubmed] Chloride channel inhibition improves neuromuscular function under conditions mimicking neuromuscular disorders

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Acta Physiol (Oxf). 2021 May 22:e13690. doi: 10.1111/apha.13690. Online ahead of print.

ABSTRACT

AIM: The skeletal muscle Cl- channels, the ClC-1 channels, stabilize the resting membrane potential and dampen muscle fibre excitability. This study explored whether ClC-1 inhibition can recover nerve-stimulated force in isolated muscle under conditions of compromised neuromuscular transmission akin to disorders of myasthenia gravis and Lambert-Eaton syndrome.

METHODS: Nerve-muscle preparations were isolated from rats. Preparations were exposed to pre-or post-synaptic inhibitors (ω-agatoxin, elevated extracellular Mg2+ , α-bungarotoxin or tubocurarine). The potential of ClC-1 inhibition (9-AC or reduced extracellular Cl- ) to recover nerve-stimulated force under these conditions was assessed.

RESULTS: ClC-1 inhibition recovered force in both slow-twitch soleus and fast-twitch EDL muscles exposed to 0.2 µM tubocurarine or 3.5 mM Mg2+ . Similarly, ClC-1 inhibition recovered force in soleus muscles exposed to α-bungarotoxin or ω-agatoxin. Moreover, the concentrations of tubocurarine and Mg2+ required for reducing force to 50 % rose from 0.14±0.02 µM and 4.2±0.2 mM in control muscles to 0.45±0.03 µM and 4.7±0.3 mM in muscles with 9-AC, respectively (P

Source: https://pubmed.ncbi.nlm.nih.gov/3402170 ... 9&v=2.14.4