Spatial non-uniformity of excitation-contraction coupling can enhance arrhythmogenic-delayed afterdepolarizations in rat cardiac muscle

Abstract

We examined whether non-uniform muscle contraction affects delayed afterdepolarizations (DADs) by dissociating Ca(2+) from myofilaments within the border zone (BZ) between contracting and stretched regions. Force, sarcomere length (SL), membrane potential, and [Ca(2+)](i) dynamics were measured in 31 ventricular trabeculae from rat hearts. Non-uniform muscle contraction was produced by exposing a restricted region of muscle to a jet of solution containing 20 mmol/L 2,3-butanedione monoxime (BDM). DADs were induced by 7.5 s-2 Hz stimulus trains at an SL of 2.0 microm (24 degrees C, [Ca(2+)](o) 2.0 mmol/L). The BDM jet enhanced DADs (n = 6, P < 0.05) and aftercontractions (n = 6, P < 0.05) with or without 100 micromol/L streptomycin and occasionally elicited an action potential. A stretch pulse from an SL of 2.0 microm to 2.1 or 2.2 microm during the last stimulated twitch of the trains accelerated Ca(2+) waves in proportion to the increment of force by the stretch (P < 0.01) with or without streptomycin. In the presence of 1 mmol/L caffeine, rapid shortening of the muscle after the stretch pulse increased [Ca(2+)](i) within the BZ, whose amplitude correlated with the increment of force by the stretch (n = 15, P < 0.01). These results suggest that non-uniform muscle contraction can enhance DADs by dissociating Ca(2+) from myofilaments within the BZ and thereby cause triggered arrhythmias.