Postnatal Changes in the Inactivation Properties of Voltage-Gated Sodium Channels Contribute to the Mature Firing Pattern of Spinal Motoneurons

Abstract

Most mammals are born with the necessary spinal circuitry to produce a locomotor-like pattern of neural activity. However, rodents seldom demonstrate weight-supported locomotor behavior until the second or third postnatal week, possibly due to the inability of the neuromuscular system to produce sufficient force during this early postnatal period. As spinal motoneurons mature they are seen to fire an increasing number of action potentials at an increasing rate, which is a necessary component of greater force production. The mechanisms responsible for this enhanced ability of motoneurons are not completely defined. In the present study we assessed the biophysical properties of the developing voltage-gated sodium current to determine their role in the maturing firing pattern. Using dissociated postnatal lumbar motoneurons in short-term culture (18–24 h) we demonstrate that currents recorded from the most mature postnatal age group (P10–P12) were significantly better able to maintain channels in an available state during repetitive stimulation than were the younger age groups (P1–P3, P4–P6, P7–P9). This ability correlated with the ability of channels to recover more quickly and more completely from an inactivated state. These age-related differences were seen in the absence of changes in the voltage dependence of channel gating. Differences in both closed-state inactivation and slow inactivation were also noted between the age groups. The results indicate that changes in the inactivation properties of voltage-gated sodium channels are important for the development of a mature firing pattern in spinal motoneurons.