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1. The effect of changes in the pH of the extracellular solution on the membrane conductance of frog sartorius and toe muscle fibres was measured with intracellular micro-electrodes.

2. In Ringer solution the membrane conductance was found to be highly sensitive to changes in pH between 5·0 and 9·8. In alkaline solution the conductance rose; in acid solution it fell.

3. After replacement of chloride by the relatively impermeant methylsulphate ion the membrane conductance showed little change when pH was altered. It is concluded that chloride is the ion species principally concerned in the pH sensitivity of the resting membrane conductance.

4. The relation between pH and the chloride conductance was sigmoid, with the steepest part of the curve lying in the region of neutrality.

5. The membrane conductance of muscles equilibrated in a 100 mM-K 216 mM-Cl solution was also sensitive to changes of extracellular pH. As in Ringer solution, the membrane conductance rose in alkaline and fell in acid solutions in a sigmoid fashion.

6. Sartorius muscles in isotonic potassium methylsulphate solution showed no change in membrane conductance at different pH values.

7. In chloride-free solution a fall in pH tended to cause depolarization; a rise in pH had the opposite effect.

8. In Ringer solution the initial effect of a rise in pH was usually a transient depolarization. The indication is that the intracellular concentration of chloride ions may be slightly in excess of that which corresponds to the resting potential. The long-term effects of changes in pH on the membrane potential in Ringer solution were in the same direction as in the absence of chloride.

9. The transient potential changes produced on addition and withdrawal of chloride ions were found to be larger in alkaline solutions than in acid solutions. This is further evidence for a higher chloride permeability in alkaline solutions.

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