In myotonia, reduced Cl⁻ conductance of the mutated ClC-1 channels causes hindered muscle relaxation after forceful voluntary contraction due to muscle membrane hyperexcitability. Repetitive contraction temporarily decreases myotonia, a phenomena called “warm up.” The underlying mechanism for the reduction of hyperexcitability in warm-up is currently unknown. Since potassium displacement is known to reduce excitability in, for example, muscle fatigue, we characterized the role of potassium in native myotonia congenita (MC) muscle. Muscle specimens of ADR mice (an animal model for low gCl⁻ conductance myotonia) were exposed to increasing K⁺ concentrations. To characterize functional effects of potassium ion current, the muscle of ADR mice was exposed to agonists and antagonists of the big conductance Ca²⁺-activated K⁺ channel (BK) and the voltage-gated Kv7 channel. Effects were monitored by functional force and membrane potential measurements. By increasing [K⁺]₀ to 5 mM, the warm-up phenomena started earlier and at [K⁺]₀ 7 mM only weak myotonia was detected. The increase of [K⁺]₀ caused a sustained membrane depolarization accompanied with a reduction of myotonic bursts in ADR mice. Retigabine, a Kv7.2–Kv7.5 activator, dose-dependently reduced relaxation deficit of ADR myotonic muscle contraction and promoted the warm-up phenomena. In vitro results of this study suggest that increasing potassium conductivity via activation of voltage-gated potassium channels enhanced the warm-up phenomena, thereby offering a potential therapeutic treatment option for myotonia congenita.

在肌强直，减少氯^-的突变CLC-1信道的原因电导受阻有力自主收缩后肌肉松弛由于肌肉膜过度兴奋。反复收缩会暂时减少肌强直，这种现象称为“热身”。目前尚不清楚降低预热时过度兴奋性的潜在机制。由于已知钾置换会降低例如肌肉疲劳的兴奋性，因此我们表征了钾在天然先天性肌强直（MC）肌肉中的作用。ADR小鼠的肌肉样品（动物模型为低GCL ^-电导肌强直）暴露于增钾⁺浓度。为了表征钾离子电流的功能效应，将ADR小鼠的肌肉暴露于大电导Ca ²⁺激活的K ⁺通道（BK）和电压门控的Kv7通道的激动剂和拮抗剂。通过功能力和膜电位测量监测效果。通过将[K ⁺ ] ₀增加到5 mM，预热现象更早开始，并且在[K ⁺ ] ₀ 7 mM时仅检测到弱肌强直。增加[K ⁺ ] ₀引起持续的膜去极化，同时减少ADR小鼠的肌强直爆发。瑞替加滨，一种Kv7.2–Kv7.5激活剂，剂量依赖性地减少了ADR强直性肌收缩的松弛缺陷，并促进了热身现象。这项研究的体外结果表明，通过激活电压门控钾通道来增加钾电导率可增强热身现象，从而为先天性肌强直提供了潜在的治疗选择。