Ion Channel Trafficking: Control of Ion Channel Density as a Target for Arrhythmias?
Ventricular myocytes are continuously exposed to fluid shear in vivo by relative movement of laminar sheets and adjacent cells. Preliminary observations have shown that neonatal myocytes respond to fluid shear by increasing their beating rate, which could have an arrhythmogenic effect under elevated shear conditions. The objective of this study is to investigate the characteristics of the fluid shear response in cultured myocytes and to study selected potential mechanisms. Cultured neonatal rat ventricular myocytes that were spontaneously beating were subjected to low shear rates (5–50/s) in a fluid flow chamber using standard culture medium. The beating rate was measured from digital microscopic recordings. The myocytes reacted to low shear rates by a graded and reversible increase in their spontaneous beating rate of up to 500%. The response to shear was substantially attenuated in the presence of the β-adrenergic agonist isoproterenol (by 86±8%), as well as after incubation with integrin-blocking RGD peptides (by 92±8%). The results suggest that the β-adrenergic signaling pathway and integrin activation, which are known to interact, may play an important role in the response mechanism.