Experimental Validation of a Closed-Loop Respiratory Control Model using Dynamic Clamp.

Abstract

We have previously introduced a model for closed-loop respiratory control incorporating an explicit conductance-based model of bursting pacemaker cells driven by hypoxia sensitive chemosensory feedback. Numerical solution of the model equations revealed two qualitatively distinct asymptotically stable dynamical behaviors: one analogous to regular breathing (eupnea), and a second analogous to pathologically rapid, shallow breathing (tachypnea). As an experimental test of this model, we created a hybrid in vitrolin silico circuit. We used Real Time eXperimental Interface (RTXI) dynamic clamp to incorporate a living pacemaker cell recorded in vitro into a numerical simulation of the closed-loop control model in real time. Here we show that the hybrid circuit can sustain the same bistable behavior as the purely computational model, and we assess the ability of the hybrid circuit to recover from simulated bouts of transient hypoxia.