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1. The effects of increasing the inspired CO₂ concentration on the transmembrane resting potential (RP), intracellular electrolytes, and cell pH of rat liver and muscle were studied.

2. Elevation of CO₂ produced a rapid reversible fall in hepatic RP. This effect is mediated by a decrease in plasma pH and is in part due to hypoxia.

3. The decrease in hepatic RP could not be accounted for by shifts in electrolytes, and an effect on membrane permeability is suggested.

4. The hepatic RP was also found to be decreased by hypoxia and increased by hyperoxia.

5. Muscle RP showed no immediate change in response to CO₂ but after 60 min there was significant depolarization. This effect could be accounted for on the basis of electrolyte shifts between cells and plasma, by use of the Goldman equation.

6. Cell pH data showed that liver is buffered approximately threefold more than skeletal muscle.

7. While intracellular pH fell in response to CO₂ the H⁺ gradient remained constant in muscle and increased in liver.