Role of Na+ and Ca2+ currents in computational model of in-vitro sigh generation
© Toporikova and Thoby-Brisson 2015
Published: 18 December 2015
The model reproduces basic features of simultaneous sigh and eupnea generation: two types of bursts differing in terms of shape, amplitude and frequency of occurrence and mimics the effect of glycinergic synapses blockade. We designed a two-compartment computational model for sigh and eupnea subpopulations of neurons with several different parameters reflecting distinct burst generating mechanisms. The sigh subpopulation generates a low frequency rhythm based on slow intracellular Ca2+ oscillations and the eupnea subnetwork generates fast oscillations mainly driven by activation/inactivation of the persistent Na+ current (Fig 1 B,C).Furthermore, we used this model to make predictions that were subsequently tested on the isolated preBötC in brainstem slice preparations. Through a combination of our in vitro and in silico approaches we found that 1), sigh events are less sensitive to network excitability than eupneic activity, 2)The combination of voltage-gated calcium current and persistent sodium current control the sigh period of, and 3), specific parameters of Ih activation set the low sensitivity to excitability in the sigh neuronal subset. Altogether, our results strongly support the hypothesis that distinct subpopulations within the preBötC network are responsible for sigh and eupnea rhythmogenesis.
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