RECIPROCAL ROLE OF THE INWARD CURRENTS IB, NA AND IF IN CONTROLLING AND STABILIZING PACEMAKER FREQUENCY OF RABBIT SINOATRIAL NODE CELLS

Experiments and computations were done to clarify the role of the various inward currents in generating and modulating pacemaker frequency. Ionic currents in rabbit single isolated sino-atrial SA) node cells were measured using the nystatin-permeabilized patch-clamp technique. The results were used to refine the Noble-DiFrancesco-Denyer model of spontaneous pacemaker activity of the SA node. This model was then used to show that the pacemaker frequency is relatively insensitive to the magnitude of the sodium-dependent inward background current i(b,Na). This is because reducing i(b,Na) hyperpolarizes the cell and so activates more hyperpolarizing-activated current, i(f), whereas the converse occurs when i(b,Na) is increased. The result is that i(f) and i(b,Na) replace one another and so stabilize nodal pacemaker frequency.