Effects of persistent sodium current blockade in respiratory circuits depend on the pharmacological mechanism of action and network dynamics
Fig 9
Comparison of experimental (colored) and simulated (black) effects of (A) TTX and (B) RZ application in the pre-BötC on the amplitude and frequency of pre-I network oscillations.
Experimental data was adapted from [9] and shows the progressive change in amplitude and frequency of network oscillations (monitored by integrated hypoglossal nerve activity) relative to baseline following bilateral microinfusion of TTX or RZ at different concentrations into the pre-BötC. The experimental data points represent the network frequency and amplitude plotted at successive 1 minute intervals after TTX or RZ application. The corresponding data points from simulated TTX and RZ application represent network frequency and amplitude for increasing levels of blockade. Simulated RZ application affects INaP and excitatory synapses whereas TTX only affects INaP. In the simulations, the relevant values at the end points (where network oscillations stop) are as follows: (A) gNaP = 3.52; (B) (top trace) Δh1/2 = −5.0 mV, WmaxE = 0.0255 nS, (bottom trace) Δh1/2 = −4.5 mV, WmaxE = 0.0224 nS. Notice that TTX only affects frequency, whereas RZ affects frequency and amplitude. (a1, b1, b2) Effect of simulated TTX and RZ (tunings 1 & 2) blockade on the peak INaP, peak ISyn, and the INaP inactivation threshold () required to initiate bursting.
was defined as the maximal value of the mean population hNaP prior to burst initiation.