High sensitivity of spontaneous spike frequency to sodium leak current in a Lymnaea pacemaker neuron.

The spontaneous rhythmic firing of action potentials in pacemaker neurons depends on the biophysical properties of voltage-gated ion channels and background leak currents. The background leak current includes a large K+ and a small Na+ component. We previously reported that a Na+ -leak current via U-type channels is required to generate spontaneous action potential firing in the identified respiratory pacemaker neuron, RPeD1, in the freshwater pond snail Lymnaea stagnalis. We further investigated the functional significance of the background Na+ current in rhythmic spiking of RPeD1 neurons. Whole-cell patch-clamp recording and computational modeling approaches were carried out in isolated RPeD1 neurons. The whole-cell current of the major ion channel components in RPeD1 neurons were characterized, and a conductance-based computational model of the rhythmic pacemaker activity was simulated with the experimental measurements. We found that the spiking rate is more sensitive to changes in the Na+ leak current as compared to the K+ leak current, suggesting a robust function of Na+ leak current in regulating spontaneous neuronal firing activity. Our study provides new insight into our current understanding of the role of Na+ leak current in intrinsic properties of pacemaker neurons.