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Departments of Neurology and Neuroscience, Case Western Reserve University School of Medicine, Louis Stokes Cleveland Veterans Affairs Medical Center, University Hospitals of Cleveland, Cleveland, Ohio 44106
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 (INa) 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. INa 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.
mammalian skeletal muscle; sodium channel; sodium current; fast inactivation; slow inactivation; paramyotonia congenita; hyperkalemic periodic paralysis
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