Reduced excitability and the safety margin in human axons during hyperthermia

Hyperthermia challenges the nervous system's ability to transmit action potentials faithfully. Neuromuscular diseases, particularly those involving demyelination have impaired safety margins for axonal generation and propagation, and symptoms are commonly accentuated by elevations in temperature. The aim of this study was to examine the mechanisms responsible for reduced excitability during hyperthermia in both motor and sensory axons. Recordings of axonal excitability were performed at normal temperatures and during focal hyperthermia for motor and sensory axons in six healthy subjects. The results show a marked decrease in excitability during hyperthermia, with reduced superexcitability following an action potential, faster accommodation to long-lasting depolarization and reduced accommodation to hyperpolarization. An existing model of human motor and sensory axons was used to model the effects of hyperthermia. The modelling suggested that slow K⁺ channels play a significant role in reducing excitability during hyperthermia. The further hyperpolarization of the activation of I _h could limit its ability to counter the hyperpolarization produced by activity, thereby allowing conduction block to occur during hyperthermia.