Abstract 11795: Structural Remodelling in Cardiomyocytes from Infarcted Hearts Potentiates Cellular Mechano-Aarrhythmic Response to Nanoscale Sarcolemmal Perturbation
After myocardial infarction (MI), structural remodelling and mechanical stress may be arrhythmogenic. We tested the hypothesis that, in hypertrophic cardiomyocytes (CMs) from infarcted hearts, local nanometre mechanical perturbation of the sarcolemma initiates and potentiates abnormal spontaneous Ca2+ activity. We use a unique combination of scanning ion conductance microscopy (SICM) modified for applying local nanometre hydrojets, in conjunction with optical recording of cytoplasmic Ca2+ levels. The SICM's nano-pipette scans the membrane of healthy adult CMs, and CMs derived from adult rats 4 and 8 weeks after coronary ligation (compensated post MI hypertrophy (MI-LVH)) superfused with Hank's solution at 36°C. The scan produces a high-resolution topographical image (Fig. A-C) and via the same pipette, a 20kPa hydro-mechanical jet of Hank's solution is applied to a restricted 400nm2 area targeting selected sarcolemmal locations for a 2 second pulse. During the pulse, and the subsequent 6 seconds, we monitor Ca2+ levels. Hydrojets applied to crests in healthy CMs did not activate Ca2+; but over the Z-grooves (Fig. B) produced short Ca2+ activations (197±29 ms in 16% of CMs, n=20) confined to the jet site. Membrane indentations during jets were 0.032±0.01 μm/kPa on crest and 0.012±0.005 μm/kPa over Z-grooves. Jets applied to unstriated MI-LVH CMs (Fig. C-D) activated longer Ca2+ transients, initiated by a ripple effect from the jet site and propagated along the entire cell (MI-4 weeks; 460±138 ms, n=11, MI-8-weeks; 499±77 ms, n=8) in 22% and 63% of the cells respectively. Membrane indentations in MI-LVH CMs were reduced (0.012±0.001 μm/kPa and 0.011±0.0025 μm/kPa). In conclusion, MI-LVH-CMs are prone to abnormal Ca2+ activations induced by local mechanical membrane perturbation, whereas normal CMs are not; these findings support the concept of mechano-arrhythmia and suggest that monitoring cardiac stiffness and elasticity may aid arrhythmia risk profiling.
- © 2011 by American Heart Association, Inc.