Modelling the Effects of Fibroblasts on the Cardiac Pacemaker

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Abstract

Cardiac fibroblasts are by number the largest component of the non-myocytes, providing structural support for the heart by regulating the synthesis and degradation of extracellular matrix components. Experimental studies suggested that they are electrically coupled to myocytes and participate in the electrical activity. The aim of this study was to provide insights into the electrophysiological role of fibroblasts in cardiac pacemaking activity at single cell level by using mathematical models and computational simulations. The simulations in the central SAN showed that the myocyte-fibroblast coupling 1) shortened action potential duration, 2) shortened cycle length, 3) decreased the maximum upstroke velocity, 4) produced more hyperpolarised maximum diastolic potential, and 5) reduced the peak value of the action potential. Since the coupling in the centre of the SAN was sensitive to the gap junctional conductance, myocytes could just couple to a fibroblast with a junctional conductance less than 0.169 nS. The coupling in the peripheral SAN showed that 1) at weak coupling (<0.13 nS), the coupling effects were similar to those in the central SAN, leading to a speeding up in the firing rate; 2) At higher coupling (>0.13 nS), there was a reduction in the peak value of the action potential and the maximum upstroke velocity, and an increase in the cycle length and a more hyperpolarised maximum diastolic potential, resulting in a slowing down in the firing rate. Whether the pacemaking rate was accelerated or decelerated, the driving ability was actually impaired as the maximum upstroke velocity and the amplitude of potential were decreased in both cases.

Keyword(s)

cardiac pacemaker; fibroblast

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