| First Author | Denman K | Year | 2026 |
| Journal | Muscle Nerve | Volume | 73 |
| Issue | 4 | Pages | 663-667 |
| PubMed ID | 41550072 | Mgi Jnum | J:379955 |
| Mgi Id | MGI:8289342 | Doi | 10.1002/mus.70158 |
| Citation | Denman K, et al. (2026) Efficacy of Retigabine in Treating Weakness in a Mouse Model of Hypokalemic Periodic Paralysis. Muscle Nerve |
| abstractText | INTRODUCTION/AIMS: Hypokalemic periodic paralysis (HypoKPP) is an ion channelopathy causing episodic skeletal muscle weakness triggered by hypokalemia. Reduced inward rectifier K(+) (Kir) channel activity contributes to membrane depolarization and paralysis, suggesting that pharmacologic activation of muscle K(+) channels may restore excitability. The Kv7 channel agonist retigabine previously mitigated low-K(+) weakness in HypoKPP models. Here, we tested whether this effect persists under conditions producing sustained, severe weakness. METHODS: Extensor digitorum longus (EDL) muscles from mice homozygous for the SCN4A R669H mutation were studied by isometric twitch force recording at 34 degrees C, with or without 20 U/L insulin. Weakness was induced by reducing extracellular K(+) to 1.0 mM. Retigabine (10 muM) was applied to the bath, and twitch force was analyzed by paired or unpaired t tests (n = 4-7 per group). RESULTS: Baseline twitch force in 4.75 mM K(+) was ~50% lower in HypoKPP than wild-type muscle (p = 0.01). Force declined further after 1 h in 4.75 mM K(+) (p = 0.016) and was completely lost at 1.0 mM K(+) with insulin. Retigabine significantly reduced loss of force at both 4.75 and 1.0 mM K(+) (p = 0.047 and p = 0.007, respectively). DISCUSSION: Kv7 channel activation by retigabine preserved contractile force even during sustained depolarization from severe hypokalemia. These findings extend prior work and support development of K(+) channel agonists as a therapeutic approach for HypoKPP. |
