MECHANOSENSITIVE FIBROBLASTS IN THE SINOATRIAL NODE REGION OF RAT-HEART - INTERACTION WITH CARDIOMYOCYTES AND POSSIBLE ROLE

The positive chronotropic response of the heart to stretch of the righ t atrium is one of the major mechanisms adjusting the heart rate to va riations in venous return on a beat-by-beat basis. The precise pathway of this mechano-electric feedback and its cellular basis are uncertai n. In this study, a possible contribution of mechanosensitive fibrobla sts, abundant in the sino-atrial node region, was investigated using a mathematical model of the electrical interaction of a mechanosensitiv e fibroblast and a sino-atrial pacemaker cell. Electrophysiological ev idence for a bio-electrical interaction of mechanosensitive fibroblast s with surrounding cardiomyocytes has been studied in (i) the isolated spontaneously beating atrium of rat hearts, and (ii) cell cultures of the neonatal rat heart. These investigations were performed using (i) double-barrelled floating microelectrodes for intracellular potential registrations, and (ii) the double whole cell patch-clamp technique. It was shown that cardiac fibroblasts and surrounding cardiomyocytes c an be either electrically well isolated from each other, or coupled bo th capacitively and electrotonically. The electrophysiological data ob tained were incorporated into the OXSOFT HEART program. Assuming that equivalent coupling may occur between mechanosensitive fibroblasts and sino-atrial pacemaker cells, a heterologous cell pair consisting of o ne fibroblast and one sino-atrial node myocyte connected by ten to thi rty single gap junctional channels with a conductance of 30 pS was mod elled. The model of the electrotonic interaction of these cells showed that stretch of the fibroblast during atrial diastole, simulating inc reased atrial wall tension during atrial filling, can raise the sponta neous depolarization rate of the pacemaker cell in a stretch-dependent manner by up to 24%. These results show that cardiac mechanosensitive fibroblasts could form a cellular basis for the positive chronotropic response of the heart to stretch of the right atrium.