Characteristics of single Na⁺ channels of adult human skeletal muscle

Abstract

The patch-clamp technique was used to study Na⁺ channels of human skeletal muscle. Preparations were from biopsies of quadriceps muscle from adults who were not suffering from neuromuscular diseases. Activity of Na⁺ channels was recorded from inside-out patches when the membrane potential was stepped from a holding potential of ±110mV to potential above a threshold of about ±65 mV. Single channel activity increased within minutes after hyperpolarizing the patch due to recovery from ultraslow inactivation. Up to ten Na⁺ channels were active in individual patches. Macroscopic currents were reconstructed by averaging single channel currents. The time-to-peak current declined from 1.6 ms at ±60 mV to 0.5 ms at +10 mV. The currents decayed mono-exponentially with time constants between 12.1 ms at ±60 mV and 0.4 ms at +10 mV (21°C). The conductance of single Na⁺ channels was 1.65 pS and the mean open time was voltage-dependent. At ±50 mV, the mean open time was 0.4 ms, while positive to ±10 mV it increased to values above 1 ms. In the threshold potential range, the number of openings per depolarizing pulse was larger than the number of channels under the patch-clamp pipette, indicating reopening of Na⁺ channels at this potential. Openings could be observed only rarely 10 ms after onset of depolarization and the macroscopic current produced by late openings was less than 0.1% of the peak current. Human skeletal muscle is thus suitable for investigation with the patch-clamp technique and the determination of properties of Na⁺ channels with this technique could be the basis for an assessment of possible defects of these channels in diseased muscle.