Effects of temperature on slow and fast inactivation of rat skeletal muscle Na+channels

Patch-clamp studies of mammalian skeletal muscle Na+ channels are commonly done at subphysiological temperatures, usually room temperature. However, at subphysiological temperatures, most Na+ channels are inactivated at the cell resting potential. This study examined the effects of temperature on fast and slow inactivation of Na+ channels to determine if temperature changed the fraction of Na+ channels that were excitable at resting potential. The loose patch voltage clamp recorded Na+ currents ( I Na) in vitro at 19, 25, 31, and 37°C from the sarcolemma of rat type IIb fast-twitch omohyoid skeletal muscle fibers. Temperature affected the fraction of Na+ channels that were excitable at the resting potential. At 19°C, only 30% of channels were excitable at the resting potential. In contrast, at 37°C, 93% of Na+ channels were excitable at the resting potential. Temperature did not alter the resting potential or the voltage dependencies of activation or fast inactivation. I Na available at the resting potential increased with temperature because the steady-state voltage dependence of slow inactivation shifted in a depolarizing direction with increasing temperature. The membrane potential at which half of the Na+channels were in the slow inactivated state was shifted by +16 mV at 37°C compared with 19°C. Consequently, the low availability of excitable Na+ channels at subphysiological temperatures resulted from channels being in the slow, inactivated state at the resting potential.