A study of pace‐maker potential in rabbit sino‐atrial node: measurement of potassium activity under voltage‐clamp conditions.

1. A single sucrose‐gap voltage‐clamp technique was used to control the membrane potential and to measure current in rabbit sino‐atrial (SA) strips. K+ activity in the extracellular space was simultaneously measured using K+‐selective micro‐electrodes. 2. Using double‐barrelled K+ selective micro‐electrodes it was possible to measure the time course of accumulation or depletion of K+ accompanying a single action potential without complications arising from mechanical or electrical artifacts. 3. K+ activity in the extracellular space increased during the action potential and then decreased to base‐line levels during the diastolic depolarization phase. Single beat accumulations of 0.1‐0.4 M could be measured. 4. The magnitude of accumulation or depletion of K+ depended upon the membrane potential such that K+ accumulated at potentials positive to ‐50 mV (K+ efflux greater than K+ uptake) and was depleted from the extracellular space at potentials negative to ‐50 mV (K+ efflux less than K+ uptake). 5. The rate of K+ depletion was fairly constant during the time course of a clamp step within the range of diastolic depolarization (‐55 to ‐75 mV) even though the accompanying membrane current showed marked time‐dependent kinetics. 6. The total membrane conductance measured during the time course of the diastolic depolarization or during the time course of activation of time‐dependent ‘pace‐maker’ current remained fairly constant or increased. 7. No reversal potential for the time‐dependent ‘pace‐maker’ current could be measured at EK in solutions containing 2.7, 5.4 and 8.1 mM‐K+. 8. These results do not support the turn‐off a K+ conductance as the primary mechanisms for the generation of the pace‐maker potential in SA nodal tissue; rather the results are more consistent with the idea that activation of an inward current, with large positive equilibrium potential, is responsible for pace‐making activity.