Causes

Myotonia is a group of clinically overlapping diseases caused by genetic defects in skeletal muscle itself. Muscle fibers have hyper-excitability

I.             Mutant Cl^- channels lead to myotonia congenita

§   There are > 30 allelic mutations (different defects in the same gene-CLCN1). They show dominant or recessive mode of transmission, which give rise to Thomsen and Becker type myotonia.

§   Mutants reduce or abolish the membrane Cl^- conductance. The resting membrane potential is shifted towards the Action potential (AP) threshold. So even a small stimulus can trigger an AP.

§   Without the contribution of CLC1, repolarization is slower. Na+ channels have enough time to recover from inactivation, but V_m is still high enough. So they open again to elicit a second depolarization (repetitive muscle contraction).

II.          Paramyotonia & K⁺ aggravated myotonia result from Na⁺ channels mutations 

§   Dominant mutations in gene SCN4A

§   Na_v 1.4 plays a vital role in initiation of AP.

§   Gain-of-function defects of the gene impair channel fast inactivation; Depolarization is prolonged, and so is muscle contraction.

§   10% of cases show enhanced activation of the channel. It is easier to trigger an AP.