Rate of rise of intrapulmonary CO2 drives breathing frequency in garter snakes

Garter snakes increase ventilation in response to elevated venous PCO2 without a concomitant rise in arterial PCO2 (Furilla et al. Respir. Physiol. 83: 47-60, 1991). Elevating venous PCO2 will increase the PCO2 gradient between pulmonary arterial blood and intrapulmonary gas during inspiration, leading to a greater rate of rise of intrapulmonary CO2 after inspiration. Because the lung contains CO2-sensitive receptors, I assessed the effect of the rate of rise of intrapulmonary CO2 on ventilation in unidirectionally ventilated snakes. CO2 concentration was altered using a digital gas mixer connected to a personal computer. Breathing frequency was highly correlated with the rate of rise intrapulmonary CO2 but only slightly affected by peak intrapulmonary CO2. On the other hand, tidal volume was more closely related to peak intrapulmonary CO2 than to the rate of rise of CO2. Bilateral pulmonary or cervical vagotomy nearly eliminated the ventilatory response associated with altered CO2 rise times but had little influence on the tidal volume response to the rate of rise of CO2. The mechanism whereby breathing frequency is controlled by the rate of rise of intrapulmonary CO2 is likely to originate with intrapulmonary chemoreceptors and may be important in the control of breathing during exercise.