Contribution of Persistent Sodium Currents to Spike-Frequency Adaptation in Rat Hypoglossal Motoneurons

Department of Physiology and Biophysics, University of Washington, School of Medicine, Seattle, Washington Submitted 13 August 2004; accepted in final form 7 September 2004 In response to constant current inputs, the firing rates of motoneurons typically show a continuous decline over time. The biophysical mechanisms underlying this process, called spike-frequency adaptation, are not well understood. Spike-frequency adaptation normally exhibits a rapid initial phase, followed by a slow, later phase that continues throughout the duration of firing. One possible mechanism mediating the later phase might be a reduction in the persistent sodium current ( I NaP ) that has been shown to diminish the capacity of cortical pyramidal neurons and spinal motoneurons to sustain repetitive firing. In this study, we used the anticonvulsant phenytoin to reduce the I NaP of juvenile rat hypoglossal motoneurons recorded in brain stem slices, and we examined the consequences of a reduction in I NaP on the magnitude and time course of spike-frequency adaptation. Adding phenytoin to the bathing solution ( 50 µM) generally produced a marked reduction in the persistent inward currents (PICs) recorded at the soma in response to slow, voltage-clamp triangular ramp commands (–70 to 0 mV and back). However, the same concentrations of phenytoin appeared to have no significant effect on spike-frequency adaptation even though the phenytoin often augmented the reduction in action potential amplitude that occurs during repetitive firing. The surprising finding that the reduction of a source of sustained inward current had no appreciable effect on the pattern of spike generation suggests that several types of membrane channels must act cooperatively to insure that these motoneurons can generate the sustained repetitive firing required for long-lasting motor behaviors. Address for reprint requests and other correspondence: M. D. Binder, Dept. of Physiology and Biophysics, Univ. of Washington, School of Medicine, Box 357290, Seattle, WA 98195 (E-mail: mdbinder{at}u.washington.edu )