Slow sodium channel inactivation in rat fast-twitch muscle

1. Voltage-clamp Na+ currents (INa) were measured in rat fast-twitch fibres using the loose-patch-clamp technique. Changes in the conditioning membrane potential produced slow changes in the peak INa elicited by short test depolarizations, due to a slow inactivation process. 2. Inactivation was increased by application of steady depolarizing potentials and was reversed by steady hyperpolarizations. These changes in peak INa could be well fitted by single-exponential functions with time constants in the range of 1-4 min. 3. The steady-state values of the maximum peak INa at any potential could be well fitted by a function identical to the one describing the fast inactivation process. This gave a potential of -108 mV at which 50% of the channels were closed due to slow inactivation. 4. The maximum peak current densities obtained with the slow inactivation fully removed were as large as 20 mA cm-2.