Accelerators and brakes in CO2 chemosensitive neurons

Abstract

The cellular factors that determine the magnitude of the firing rate response of chemosensitive neurons to increased CO2/H+are typically attributed to acid‐induced increased firing rate pathways (accelerators). However, a marked reduction in the CO2/H+‐induced increased firing rate during postnatal development has been observed in neurons from the locus coeruleus (LC). This response has been hypothesized to be due to the development of a decelerating pathway that arises from CO2/H+ activation of Ca2+ channels, which in turn induces the Ca2+‐activation of KCa channels. In order to investigate the contribution of such a braking pathway in the magnitude of the firing rate in individual neurons, we have developed a preliminary computational model of excitable single neuron that simulates the voltage‐gated currents as well as the pH and Ca2+ sensitive K+ currents using the Hodgkin‐Huxley formulation. In our simulations we found that inhibition of the L‐type Ca2+current led to a larger hypercapnic‐induced firing rate response. These findings constitutes theoretical evidence that the cellular factors limiting the firing rate response of chemosensitive neurons are associated with acid activated Ca2+ and Ca2+ activated KCa currents, allowing us to conclude that a braking pathway may play a more significant role in setting neuronal chemosensitivity. Supported by NIH Grant HL56683.