CHARACTERISTICS OF NA+ CHANNELS AND CL- CONDUCTANCE IN RESEALED MUSCLE-FIBER SEGMENTS FROM PATIENTS WITH MYOTONIC-DYSTROPHY

1. Electrical and contractile properties of resealed fibre segments were investigated by a variety of in vitro techniques. The preparations were removed from skeletal muscles of normal subjects and of eight patients with myotonic dystrophy. 2. Several hours after removal, fibre segments from normal subjects and those patients in whom myotonia was the primary symptom had resting membrane potentials of approximately ‐80 mV. In contrast, fibre segments obtained from patients in whom muscle dystrophy was more expressed were depolarized (‐60 to ‐70 mV). 3. Contractions induced in fibre segments of myotonic muscle which had normal potentials were characterized by slowed relaxation which was due to electrical after‐activity. 4. After single stimuli, long‐lasting (3‐100) runs of action potentials were recorded intracellularly from the myotonic muscle. In some of these fibre segments complex repetitive discharges were observed: multiple sites of locally gated currents were identified. 5. The three‐electrode voltage clamp was used to determine the total membrane conductance, gm, and the ion component conductances. All fibres of a particular patient had similar conductances. However, the Cl‐ conductance varied from patient to patient from normal (74% of gm) to low values (30% of gm). The K+ conductance was normal in all fibres of all patients. 6. The patch‐clamp technique was used to record currents through single Na+ channels of the sarcolemma. After treatment of the fibre segments with collagenase gigaohm seals were routinely obtained. The rate of success was greater when using the cell‐attached mode than the inside‐out mode. 7. Sodium channel currents were elicited by depolarizing voltage steps which produced an initial burst of Na+ channel openings. Up to ten channels were activated simultaneously when the patch was depolarized to potentials more positive than ‐30 mV. The Na+ channels re‐opened very rarely in controls. The macroscopic sodium current, INa, was reconstructed by averaging depolarizing pulses. The time constant of rapid decay of INa reflecting macroscopic inactivation, the onset of INa and the amplitude of INa were voltage dependent. The mean amplitude of the current produced by re‐openings was on average only 0.11 +/‐ 0.04% of the amplitude of the peak current. 8. Late openings of the Na+ channels were frequent in patches on the myotonic fibre segments. The amplitude of the current produced by re‐openings was as high as about 0.75 +/‐ 0.11% of the amplitude of the peak current.(ABSTRACT TRUNCATED AT 400 WORDS) © 1990 The Physiological Society