Sodium channel slow inactivation and the distribution of sodium channels on skeletal muscle fibres enable the performance properties of different skeletal muscle fibre types.

Na+ currents (INa) and membrane capacitance were studied with the loose patch voltage clamp technique and action potential properties were studied with a two-electrode voltage clamp on the end-plate, at the end-plate border and on extrajunctional membrane of skeletal muscle fibres. Slow inactivation regulates the available INa and is operative at the resting potential of both rat and human fibres. At the resting potential, slow inactivation causes a greater reduction in INa in fast-than in slow-twitch fibres. The relative resistance of slow-twitch fibres to slow inactivation may enable slow-twitch fibres to remain tonically active. Na+ channel inactivation may provide a peripheral mechanism that limits the duration that fast-twitch fibres can fire at high rates to prevent injury associated with prolonged high-frequency contraction. Consequently, slow inactivation may enable fast-twitch fibres to operate phasically at high rates or slow-twitch fibres to fire continuously at lower rates. For both fast- and slow-twitch fibres. INa normalized to membrane area was greatest on the end-plate, intermediate on the end-plate border and smallest on extrajunctional membrane. When normalized to membrane capacitance. INa was the same on the end-plate and the end-plate border and smallest on extrajunctional membrane. For a given membrane region, INa was larger on fast- than on slow-twitch fibres. The higher density of Na+ channels near the end-plate increased the safety factor for neuromuscular transmission by lowering the action potential threshold and increasing the action potential rate of rise at the end-plate.