Pulsatile stretch remodels cell-to-cell communication in cultured myocytes

Mechanical stretch is thought to play an important role in remodeling atria l and ventricular myocardium and may produce substrates that promote arrhyt hmogenesis. In the present work, neonatal mt ventricular myocytes were cult ured for 4 days as confluent monolayers on thin silicone membranes and then subjected to linear pulsatile stretch for up to 6 hours. Action potential upstrokes and propagation velocity (Theta) were measured with multisite opt ical recording of transmembrane voltage of the cells stained with the volta ge-sensitive dye RH237. Expression of the gap junction protein connexin43 ( Cx43) and the fascia adherens junction protein N-cadherin was measured immu nohistochemically in the same preparations, Pulsatile stretch caused dramat ic upregulation of intercellular junction proteins after only 1 hour and a further increase after 6 hours (Cx43 signal increased from 0.73 to 1.86 and 2.02% cell area, and N-cadherin signal increased from 1.21 to 2.11 and 2.7 4% cell area after 1 and 6 hours, respectively). This was paralleled by an increase in Theta from 27 to 35 cm/s after 1 hour and 37 cm/s after 6 hours . No significant change in the upstroke velocity of the action potential or cell size was observed. Increased Theta and protein expression were not re versible after 24 hours of relaxation. Nonpulsatile (static) stretch produc ed qualitatively similar but significantly smaller changes than pulsatile s tretch. Thus, pulsatile linear stretch in vitro causes marked upregulation of proteins that form electrical and mechanical junctions, as well as a con comitant increase in propagation velocity. These changes may contribute to arthythmogenesis in myocardium exposed to acute stretch.