Computational Model of Rabbit SA Node Pacemaker Activity Probed with Action Potential and Calcium Transient Clamp

In the past decades, various computational models of the pacemaker activity of single sinoatrial (SA) nodal cells have been developed, building on data obtained in patch-clamp experiments on isolated SA nodal myocytes. These models show widely different results regarding the contribution of individual ionic currents to diastolic depolarization and pacemaker activity of the SA nodal myocyte. Because several of these ionic currents are strongly dependent on time, voltage and/or intracellular free calcium concentration ([Ca ²⁺]_i), one may argue that the apparent differences in the contribution of a particular ionic current to pacemaker activity between SA nodal cell models reflect differences in action potential shape and calcium transient between models rather than intrinsic differences in the ionic current of interest. To better appreciate the contribution of individual ionic currents to pacemaker activity in a computational model of an SA nodal cell, we imposed a realistic action potential shape and calcium transient on the model cell. This was achieved by first simultaneously recording membrane potential and [Ca ²⁺]_i from single isolated SA nodal myocytes and then subjecting the model cell to a combined ´action potential clamp´ and ´calcium transient clamp´ using a data file with a train of experimentally recorded SA nodal action potentials and associated calcium transients. The thus computed individual ionic currents should then more closely resemble the ´true´ ionic currents during pacemaker activity of an SA nodal myocyte. Also, differences between the recorded and the computed net membrane current may prove helpful in identifying shortcomings of the computational model.