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.

Stereoselective interaction of tocainide and its chiral analogs with the sodium channels in human myoballs.

The effects of both enantiomers of tocainide and of some of its chiral analogs on the inactivation of the sodium current in human myoballs were investigated with the whole-cell recording technique. Structure and electron densities of the applied compounds were calculated and compared to the results. Both the R(-) and the S(+) enantiomers had little effect on fast inactivation determined with short prepulses according to Hodgkin and Huxley (1952; h infinity curve).

Altered sodium channel behaviour causes myotonia in dominantly inherited myotonia congenita.

The cause of increased excitability in autosomal dominant myotonia congenita (MyC) was studied in resealed greater than 3-cm long segments of muscle fibres from eight patients. Three hours after biopsy only about 50% of the fibre segments had regained a normal resting potential. This differs from our experiences with normal muscle or other disorders of myotonia (e.

K+ channel openers suppress myotonic activity of human skeletal muscle in vitro.

Isolated fibre bundles from myotonic human skeletal muscle showed after-contractions and spontaneous mechanical activity. The K+ channel openers cromakalim (10-100 mumols/l) and EMD 52962 (1-10 mumols/l) completely suppressed these abnormalities in mechanical activity. Voltage-clamp experiments revealed that cromakalim (100 mumols/l) increased the membrane K+ conductance of isolated, non-myotonic human skeletal muscle fibres 4-fold; Cl- conductance was not altered.

Inactivation of human sodium channels and the effect of tocainide.

The inactivation of the sodium channels in human medulloblastoma cells was investigated with the whole-cell recording technique. The potential dependence of inactivation ("inactivation curve") was determined by imposing a series of prepulses of varying amplitude on the membrane potential and measuring the maximum sodium current flowing after each prepulse at the test potential of -20 mV. The time dependence of inactivation was investigated by determining inactivation curves with prepulses of variable duration.