Contribution of the Na+/K+ Pump to Rhythmic Bursting, Explored with Modeling and Dynamic Clamp Analyses.

Abstract

The Na+/K+ pump, often thought of as a background function in neuronal activity, contributes an outward current (Ipump) that responds to the internal concentration of Na+ ([Na+]i). In bursting neurons, such as those found in central pattern generator (CPG) neuronal networks that produce rhythmic movements, the [Na+]i and therefore the Ipump, can be expected to vary throughout the burst cycle. This responsiveness to electrical activity, combined with independence from membrane potential, endow Ipump with dynamical properties not common to channel-based currents (e.g., voltage- or transmitter-gated or leak channels). Moreover, in many neurons, the pump's activity is modulated by a variety of modulators, further expanding the potential role of Ipump in rhythmic bursting activity. This paper shows how to use a combination of modeling and dynamic clamp methods to determine how Ipump and its interaction with persistent Na+ current influence rhythmic activity in a CPG. Specifically, this paper will focus on a dynamic clamp protocol and computational modeling methods in heart interneurons of medicinal leeches.