Muscle fatigue arising intrinsically from SUR2- but not Kir6.1-dependent gain-of-function in Cantu syndrome mice.

ABSTRACT: Cantu syndrome (CS) is a rare disease caused by gain-of-function (GOF) mutations of Kir6.1 or SUR2 subunits of ATP-sensitive potassium (KATP) channels. CS patients with SUR2 and Kir6.1 variants display a similar constellation of symptoms, including muscle weakness and fatigue. The effects of CS mutations on skeletal muscle KATP channels, and any consequent direct effects on contractility, are currently unclear. Here, we used two knock-in mouse models of CS, respectively, carrying GOF mutations Kir6.1[V65M] or SUR2[A478V], to assess KATP channel properties and contractility in isolated fast-twitch extensor digitorum longus (EDL) and slow-twitch soleus (SOL) muscles. Electrophysiological recordings in isolated myofibers showed normal resting potentials, and excised patch-clamp recordings sho

SUBMITTER: Scala R 

PROVIDER: S-EPMC12629551 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature