This is the model used throughout the paper, Parker, J., & Ramirez, J. M. (2024). Differentiating the contributions of Na+/K+ pump current and persistent Na+ current in simulated voltage-clamp experiments. Journal of neurophysiology, In Review. Included in this code is a few different versions of the model. Firstly, there is the full canonical model of a single neuron producing inspiration-like bursting or the associated bursting seen when rhythmic cells are recorded in vitro, which is much slower than actual inspiration. Second, there is a reduced version of the model where the intracellular Na+ concentration is held constant as a parameter and modified. Third, there is a model where the cell is voltage-clamped and voltage protocols are applied to measure the inactivation kinetics of persistent sodium. This part gets confusing, because the model does not actually contain an hNaP variable. You really need to read the paper to understand what is going on here. But in short, we are looking at whether the presence of Na+/K+ pump current can make the cell INaP appear to slowly inactivate. There are then 2 more versions of the voltage-clamped model, Model A and Model B, which are slight variations of the original.
Experimental motivation: Paper Abstract: The persistent Na+ current (INaP) is thought to play important roles in many brain regions including the generation of inspiration in the ventral respiratory column (VRC) of mammals. The characterization of the slow inactivation of INaP requires long-lasting voltage steps (>1 s), which will increase intracellular Na+ and activate the Na+/K+-ATPase pump current (IPump). Thus, IPump may contribute to the previously measured slow inactivation of INaP and the generation of the inspiratory bursting rhythm. To test this hypothesis, we computationally modeled a respiratory pacemaker neuron that included a non-inactivating INaP and IPump in addition to other basic spike-generating currents. This model produces an inspiration-like bursting rhythm, in which the dynamics of [Na+]i account for burst initiation and termination. We simulated a voltage-clamp experiment measuring the INaP inactivation kinetics using our model of non-inactivating INaP and IPump. Consistent with prior measurements in the VRC, we found a sigmoidal inactivation curve and a current that only partially inactivated reaching a minimum inactivation of 0.37. The biexponential time course of inactivation had decay rate constants of 0.45 s and 2.33 s with contributions of 49% and 51% respectively. The time constant of inactivation was 2.16 s. This decay was caused by the slow growth of IPump and the slow hyperpolarization of the Na+ reversal potential in response to the growing [Na+]i. We conclude that important biophysical properties previously attributed to the INaP may be caused by IPump. This has important implications for understanding respiratory rhythmogenesis and other neuronal functions.
Model Type: Neuron or other electrically excitable cell
Region(s) or Organism(s): Brainstem
Cell Type(s): Respiratory column neuron
Currents: I K,leak; I Na, leak; I Na, slow inactivation; I_KD; Na/K pump
Receptors:
Genes:
Transmitters:
Model Concept(s): Persistent activity
Simulation Environment: C or C++ program; MATLAB
References: