Bursting Dynamics Based on the Persistent Na and Na/K Pump Currents: A Dynamic Clamp Approach

Life-supporting rhythmic motor functions like heart-beating in invertebrates and breathing in vertebrates require an indefatigable generation of a robust rhythm by specialized oscillatory circuits, central pattern generators (CPGs). These CPGs should be sufficiently flexible to adjust to environmental changes and behavioral goals. Continuous self-sustained operation of bursting neurons requires intracellular Na concentration to remain in a functional range and to have checks and balances of the Na fluxes met on a cycle-to-cycle basis during bursting. We hypothesize that at a high excitability state, the interaction of the Na/K pump current, I, and persistent Na current, I, produces a mechanism supporting functional bursting. I is a low voltage-activated inward current that initiates and supports the bursting phase. This current does not inactivate and is a significant source of Na influx. I is an outward current activated by [Na] and is the major source of Na efflux. Both currents are active and counteract each other between and during bursts. We apply a combination of electrophysiology, computational modeling, and dynamic clamp to investigate the role of I and I in the leech heartbeat CPG interneurons (HN neurons). Applying dynamic clamp to introduce additional I and I into the dynamics of living synaptically isolated HN neurons in real time, we show that their joint increase produces transition into a new bursting regime characterized by higher spike frequency and larger amplitude of the membrane potential oscillations. Further increase of I speeds up this rhythm by shortening burst duration (BD) and interburst interval (IBI).