Abstract

Inotropic agents induce changes in the contraction amplitude and frequency of cardiomyocytes (CMs). However, it is unknown how local contractions of CMs treated by inotropic agents behave spatiotemporally. In this study, the effect of isoproterenol, a positive inotropic agent, on local contractions of isolated neonatal rat CMs was explored by atomic force microscopy (AFM). We observed that changes in local contraction amplitude of CM in the presence of isoproterenol were heterogeneous; they were unchanged or increased, at different positions, with respect to the amplitude of untreated CMs. Interestingly, spatial heterogeneities of local contraction amplitude of CM in the presence of isoproterenol did not obviously correlate with the local elasticity, indicating that the local contractions were facilitated by cooperative dynamics of the cytoskeletal structure in relatively large regions, rather than those just under AFM indentation. Moreover, local contraction amplitude of CM in the presence of isoproterenol was not proportional to that in the control condition, showing that the former change was no longer additive in local scales.

Keywords: Atomic force microscopy, isoproterenol, inotropic agents, neonatal cardiomyocytes, spatiotemporal contraction, elasticity, isolated neonatal, cytoskeletal structure, local scales, actin-myosin interactions, living CMs, single cells, high spatial resolution, cell images