Schwartz–Jampel syndrome: II. Na+ channel defect causes myotonia

Abstract

Skeletal muscle fibers from a patient with Schwartz–Jampel syndrome were studied in vitro. The fibers had normal resting membrane potentials, but their resting [Ca²⁺]_i was elevated. The resting potentials were unstable and spontaneous depolarizations caused twitching in all fibers. Stimulated contractions were characterized by markedly slowed relaxation which was due to electrical after-activity. Neither curare (0.7 μM), tocainide (50 μM), nor phenytoin (80 μM) had an effect on the myotonic activity. In contrast, procainamide (200 μM) suppressed the hyperexcitability without affecting the twitch amplitude. The steady-state current-voltage relation was normal in 5 fibers, but altered in 3 others. These latter fibers had an increased specific membrane resistance owing to a decreased Cl- conductance. The Na⁺ channels were investigated in the cell-attached patch clamp mode. In all patches on either type of fiber, depolarizing pulses elicited delayed, synchronized openings of Na⁺ channels. These abnormal openings occurred even after the surface membrane repolarized. We hypothesize that these altered membrane conductances are responsible for the hyperexcitability and the associated slowed relaxation.