Spatiotemporal Transitions in Cardiac Neuronal Co-Cultures

Abstract

A variety of arrhythmias have been attributed to formation of large scale patterns of excitation such as formation and break-up of spiral waves. We investigate the relationship between neuronal activity and evolution of macroscopic spatiotemporal dynamics. We also aim to understand the role of target-derived trophic nerve growth factors (NGF) on the formation and function of synapses between sympathetic neurons and heart tissue.Hearts were isolated from neonatal rat pups, ventricular myocytes were isolated, cultured and after 24h, stellate ganglia were isolated from litter mates enzymatically digested, and neurons were plated on top on myocyte dishes. We used dye-free imaging techniques using to record wave pattern and beat-rate (in the presence/absence of NGF).For the first time, we report wave speeds in cardiac neuron co-cultures. Our results show that (i) basal speed of co-cultures is significantly faster than myocyte only cultures (p<0.001); (ii) nicotine causes an altered behaviour in wave patterns; (iii) application of nicotine to co-culture causes a transient increase in contraction rate; (iv) the spatial organization of cells in myocyte monocultures is significantly altered by the addition of NGF.Our observations may be relevant to understanding how neuronal activity modulates macroscopic cardiac function. The finding that NGF modulates the development and patterning of myocytes raises the question of how NGF and their receptors interact to lead to long term changes in cardiac and synaptic function.