Effects of calcium (Ca²⁺) extrusion mechanisms on electrophysiological properties in a hypoglossal motoneuron: Insight from a mathematical model

Spike-frequency dynamics and spike shape can provide insight into the types of ion channels present in any given neuron and give a sense for the precise response any neuron may have to a given input stimulus. Motoneuron firing frequency over time is especially important due to its direct effect on motor output. Of particular interest is intracellular Ca²⁺, which exerts a powerful influence on both firing properties over time and spike shape. In order to better understand the cellular mechanisms for the regulation of intracellular Ca²⁺ and their effect on spiking behavior, we have modified a computational model of an HM to include a variety of Ca²⁺ handling processes. For the current study, a series of HM models that include Ca²⁺ pumps, Na⁺/Ca²⁺ exchangers, and a generic exponential decay of excess Ca²⁺ were generated. Simulations from these models indicate that although each extrusion mechanism exerts a similar effect on voltage, the firing properties change distinctly with the inclusion of additional Ca²⁺-related mechanisms: BK channels, Ca²⁺ buffering, and diffusion of [Ca²⁺]_i modeled via a linear diffusion partial differential equation. While an exponential decay of Ca²⁺ seems to adequately capture short-term changes in firing frequency seen in biological data, internal diffusion of Ca²⁺ appears to be necessary for capturing longer term frequency changes.