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

Abstract

AbstractLife-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, Ipump, and persistent Na+current, INaP, produces a mechanism supporting functional bursting. INaPis 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. Ipumpis an outward current activated by [Na+]iand 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 Ipumpand INaPin the leech heartbeat CPG interneurons (HN neurons). Applying dynamic clamp to introduce additional Ipumpand INaPinto 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 Ipumpspeeds up this rhythm by shortening burst duration (BD) and interburst interval (IBI).