Reduced K+ build-up in t-tubules contributes to resistance of the diaphragm to myotonia

Patients with myotonia congenita suffer from slowed muscle relaxation caused by hyperexcitability. The diaphragm is only mildly affected in myotonia congenita; discovery of the mechanism underlying its resistance to myotonia could identify novel therapeutic targets. Intracellular recordings from two mouse models of myotonia congenita revealed the diaphragm had less myotonia than either the EDL or the soleus muscles. A mechanism contributing to the resistance of the diaphragm to myotonia was reduced depolarisation of the interspike membrane potential during repetitive firing of action potentials, a process driven by the build-up of K+ in small invaginations of muscle membrane known as t-tubules. We explored differences between diaphragm and EDL that might underlie the reduction of K+ build-up in diaphragm t-tubules. A smaller size of diaphragm fibres, which promotes the diffusion of K+ out of t-tubules was identified as a contributor. Intracellular recording revealed slower repolarizatio..., Intracellular and force recordings recordings were performed. Data was collected using a CED 1401 A to D board using Spike2 software (Cambridge Electronic Design Limited). No filtering was applied to the signal., , # Reduced K+ build-up in t-tubules contributes to resistance of the diaphragm to myotonia

[https://doi.org/10.5061/dryad.5mkkwh7dx](https://doi.org/10.5061/dryad.5mkkwh7dx)

These data are from a mouse model of myotonia congenita.  

## Description of the data and file structure

For muscle force recordings we used the genetic model of myotonia congenita as we found the severity of myotonia changed over time when myotonia was triggered by block of Cl- channels with 100 µM 9-anthracenecarboxylic acid (9AC, the pharmacologic model of myotonia congenita) (Palade and Barchi 1977). The genetic mouse model of myotonia congenita used was *Clcn1adr-mto*/J (ClCadr) mice, which have a homozygous null mutation in the *Clcn1* gene (Jackson Labs cat #000939).

For intracellular recordings 9AC was applied to trigger myotonia. This allowed us to avoid the need for a large breeding colony to produce the requisite number of recessive *Clcn1* mutants. Intracellular recordings were made from surface fibr...