On the mechanism by which changes in extracellular pH affect the electrical activity of the rabbit sino-atrial node.

1. The effect of altering the extracellular pH (pHo) on the electrical activity of the isolated rabbit sino-atrial (s.a.) node was studied using the two-micro-electrode voltage-clamp technique. 2. Alkalinization of the perfusate increased the maximum rate of rise and amplitude of the nodal action potential, and also the frequency of spontaneous beating of the s.a. node; acidification produced opposite effects. 3. A change in the extracellular pH from a value of 6.5 to 8.5 caused increases of the maximal conductance for both the slow inward current and the steady-state outward current systems without affecting the gating processes of the channels. 4. H+ could modify the electrical activity of s.a. nodal cells, not through altering the membrane surface potential but through the protonation of the ionic channels themselves. From the titration curves, the apparent pKa values for the slow inward current and the steady-state outward current were estimated to be 6.4 and 6.0, respectively.