Ionic currents responsible for the generation of pace‐maker current in the rabbit sino‐atrial node.

The ionic nature of the pace‐maker current (delta Ip, If, Ih) was investigated in rabbit sino‐atrial node using a single sucrose‐gap voltage‐clamp technique. The pace‐maker current was activated by hyperpolarizing clamp steps negative to ‐50 mV and the pace‐maker potential was activated by an action potential or a depolarizing clamp step. Neither pace‐maker current nor pace‐maker potential were altered by addition of tetrodotoxin, but a tetrodotoxin‐sensitive channel could be activated in sino‐atrial nodal strips following hyperpolarizing clamp steps. Ca2+‐channel blockers did not affect the voltage dependence of delta Ip or the maximum diastolic potential (m.d.p.) significantly. Removal of Ca2+ did not affect the pace‐maker current at clamp potentials near the pace‐maker potential range (‐60 to ‐80 mV), but it did reduce the potential dependence of the m.d.p. Removal of Na+ suppressed completely the pace‐maker current and hyperpolarized the membrane. Removal of Na+ also increased membrane conductance, most likely through an increase in resting K+ permeability. Low concentration of Cs+ (less than 5 mM), but not Ba2+ or tetraethylammonium, markedly suppressed activation delta Ip and reduced the rate of pacing slightly. Cs+ also decreased the membrane conductance and hyperpolarized the membrane. In 50% of experiments designed to determine contribution of IK to pace‐maker current, a double‐pulse procedure revealed a time‐dependent component of delta Ip which reversed near the K+ equilibrium potential, EK. Release of depolarizing or hyperpolarizing test clamps was followed by pace‐maker potentials, the magnitudes of which were dependent on the test‐clamp potential. The m.d.p. approached values near EK following depolarizing clamps and near ‐45 mV following hyperpolarizing clamps. The results suggest that delta Ip is carried primarily by Na+ and is blocked by Cs+. It is likely, however, that Ca2+ alters the rate of pacing not only through its contribution to the Isi system, but also through activation of a K+ conductance.