A simulation of ventilatory responses to infused and inhaled CO2 at controlled cardiac output and high and low levels of neural excitation mimics comparable experiments in animals. The model suggests that at low levels of endogenous and exogenous CO2 load the alert quiescent animal will show hyperpnea to both test states associated with hypercapnia. The nonalert quiescent animal simulated will show an isocapnic response to endogenous load and hypercapnic response to exogenous load. The explanation of this behavior lies in the model formulation, which allows the neural signal from metabolically active sources to drive the proportional component of the controller below an operating level established by its set point. By this reasoning the excited but metabolically inactive animal should be paradoxically less sensitive to small changes in CO2, whether exogenous or endogenous, than the quiescent animal. The model demonstrates further that a neural "exercise" signal in proportion to venous return better simulates observations in which CO2 load and venous return are dissociated than one in which the neural signal is computed from metabolism. The use of delta V/delta P slopes as estimates of sensitivity go awry in experiment and simulation when blood flow, CO2 level, and neural excitatory state are dissociated. This is particularly true when the organism is operating at and below the hypothesized set point.
Selective Adrenergic/Cyclic AMP-Dependent Switch-Off of Proteasomal Proteolysis Alone Switches on Neural Signal Transduction