Altered Na⁺ channel activity and reduced Cl⁻ conductance cause hyperexcitability in recessive generalized myotonia (becker)

Intact muscle fibers or resealed fiber segments from 7 patients with recessive generalized myotonia were studied in vitro. All fibers had normal resting membrane potentials and normal resting [Ca²⁺]_i several hours after removal. Contractions were characterized by slowed relaxation which was due to electrical after‐activity. Often spontaneous depolarizations were recorded intracellularly. In all fibers, the steady state voltage‐current relationship was abnormal, due to a reduced Cl²⁺ conductance. However, this conductance ranged from 0% to 66% of the total membrane conductance, whereas, in normal muscle, it was 80%. Theoretically, myotonic after‐discharges would not appear until the Cl⁻ conductance is below 20%. Thus, the membrane hyperexcitability must be due to another defect, at least in the preparations in which the Cl⁻ conductance was only slightly reduced. In all patches from all patients investigated with the patch clamp technique, we observed reopenings of the Na⁺ channels throughout depolarizing pulses (such behavior was absent in normal muscle). If a patch was polarized to potentials less negative than the resting potential, the duration of the reopenings increased. We conclude that a combination of reduced Cl⁻ conductance and the reopenings of Na⁺ channels underlie the electrical afteractivity in recessive generalized myotonia.