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 hy-pothesize that at a high excitability state, the interaction of the Na+/K+ pump current, Ipump, and persistent Na+ current, INaP, produces a mechanism supporting functional bursting. INaP 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. Ipump is an outward current activated by [Na]+i and is the major source of Na+ efflux. Both currents are ac-tive and counteract each other between and during bursts. We apply a combination of electrophysiology, compu-tational modeling, and dynamic clamp to investigate the role of Ipump and INaP in the leech heartbeat CPG interneurons (HN neurons). Applying dynamic clamp to introduce additional Ipump and INaP into the dynamics of liv-ing 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 oscilla-tions. Further increase of Ipump speeds up this rhythm by shortening burst duration (BD) and interburst interval (IBI).