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

Abstract

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_pump, and persistent Na⁺ current, I_NaP, produces a mechanism supporting functional bursting. I_NaP 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_pump is an outward current activated by [Na⁺]_i 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_pump and I_NaP in the leech heartbeat CPG interneurons (HN neurons). Applying dynamic clamp to introduce additional I_pump and I_NaP 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_pump speeds up this rhythm by shortening burst duration (BD) and interburst interval (IBI).

Keywords: bursting neuron; central pattern generator; electrophysiology; interneuron; intracellular Na+ concentration; invertebrate; oscillatory networks.