Pacemaking in rabbit isolated sino-atrial node cells during Cs+ block of the hyperpolarization-activated current if.

1. Experiments have been carried out using the whole-cell patch clamp technique to investigate how the spontaneous pacemaker activity of rabbit isolated sino-atrial (SA) node cells is affected by the block of the hyperpolarization-activated current if by 1 and 2 mM-caesium. 2. Two millimolar caesium reduced the amount of if activated at -90 mV to less than 10% of the control value. In the pacemaking range of SA node cells, if was often completely blocked by this concentration of Cs+. 3. Two millimolar caesium slowed but did not arrest spontaneous pacemaking in isolated SA node cells. In freely beating non-patched cells, 2 mM-CsCl caused a 30% reduction in rate of beating, indicating that in all cells observed if was normally contributing to pacemaking. 4. No increase in instantaneous inward current was seen in response to hyperpolarizing voltage clamp pulses from a holding potential of -40 mV when 1 or 2 mM-CsCl was applied to SA node cells. These concentrations of Cs+ do not therefore induce an 'extra' inward current. 5. Neither the inward calcium current (iCa) nor the outward potassium current (iK) showed changes which could be attributed to Cs+ application. 6. Since spontaneous pacemaking continues during Cs+ block of if while other membrane currents show no Cs(+)-induced changes which could account for this, these experiments provide strong, though indirect, evidence for the presence in SA node of a time-independent background current, ib, which will contribute to a mode of pacemaking controlled by the decay of potassium conductance (gK). The nature of this inward current has yet to be clarified. 7. The results strongly suggest that the hyperpolarization-activated current if normally makes an important contribution to the pacemaker depolarization of all SA node cells.