Mechanoelectrical excitation by fluid jets in monolayers of cultured cardiac myocytes

Abstract

Kong, Chae-Ryon, Nenad Bursac, and Leslie Tung. Mechanoelectrical excitation by fluid jets in monolayers of cultured cardiac myocytes. J Appl Physiol 98: 2328 -2336, 2005. First published February 24, 2005 doi:10.1152/japplphysiol.01084.2004.-Although the prevailing view of mechanoelectric feedback (MEF) in the heart is in terms of longitudinal cell stretch, other mechanical forces are considerable during the cardiac cycle, including intramyocardial pressure and shear stress. Their contribution to MEF is largely unknown. In this study, mechanical stimuli in the form of localized fluid jet pulses were applied to neonatal rat ventricular cells cultured as confluent monolayers. Such pulses result in pressure and shear stresses (but not longitudinal stretch) in the monolayer at the point of impingement. The goal was to determine whether these mechanical stimuli can trigger excitation, initiate a propagated wave, and induce reentry. Cells were stained with the voltage-sensitive dye RH237, and multi-site optical mapping was used to record the spread of electrical activity in isotropic and anisotropic monolayers. Pulses (10 ms) with velocities ranging from 0.3 to 1.8 m/s were applied from a 0.4-mm diameter nozzle located 1 mm above the cell monolayer. Fluid jet pulses resulted in circular wavefronts that propagated radially from the stimulus site. The likelihood for mechanical stimulation was quantified as an average stimulus success rate (ASSR). ASSR increased with jet amplitude and time waited between stimuli and decreased with the application of gadolinium and streptomycin, blockers of stretch-activated channels, but not with nifedipine, a blocker of the L-type Ca channel. Absence of cellular injury was confirmed by smooth propagation maps and propidium iodide stains. In rare instances, the mechanical pulse resulted in the induction of reentrant activity. We conclude that mechanical stimuli other than stretch can evoke action potentials, propagated activity, and reentrant arrhythmia in two-dimensional sheets of cardiac cells. mechanoelectrical coupling; ventricular arrhythmias; optical mapping; cell culture; neonatal rat NUMEROUS STUDIES have shown that mechanical stretch or load applied to a cardiac tissue can induce significant electrophysiological effects via the process termed "mechanoelectric feedback" (MEF). Mechanically triggered action potentials have been observed with sudden stretch of the ventricles (20), stretch of the isolated ventricular free wall (17), or mechanical stimulation of single cardiac myocytes (13,28,42). Mechanical stretch also changes action potential duration (42, 48, 51), excitability (45), and expression of gap junctional channels (52). The electrophysiological effects have been attributed mainly to the activity of stretch-activated ion channels (SACs) (26). Pharmacological agents that inhibit SAC activity include streptomycin (21), gadolinium (Gd 3ϩ ) (26), and the tarantula toxin .The mechanically induced premature ventricular beats mentioned above can be proarrhythmic. As a dramati...

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Shear stress triggers insertion of voltage-gated potassium channels from intracellular compartments in atrial myocytes

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