Reciprocal role of the inward currents i b, Na and i f in controlling and stabilizing pacemaker frequency of rabbit sino-atrial node cells

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Abstract
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$_{\text{b,Na}}$. This is because reducing i$_{\text{b,Na}}$ hyperpolarizes the cell and so activates more hyperpolarizing-activated current, i$_{\text{f}}$, whereas the converse occurs when i$_{\text{b,Na}}$ is increased. The result is that i$_{\text{f}}$ and i$_{\text{b,Na}}$ replace one another and so stabilize nodal pacemaker frequency.

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