Abstract 11057: Regional Increase in Extracellular Potassium Can Be Arrhythmogenic by Non-uniform Muscle Contraction in Rat Cardiac Muscle
Background: In the ischemic myocardium, extracellular potassium ([K+]o) increases to ≥20 mM and decreases muscle contraction in the region. Thus, we investigated whether this regional decrease in contraction affects the occurrence of arrhythmias.
Methods: To produce a regional increase in [K+]o, 35 rat trabeculae, each from a limited region of muscle, were exposed to a jet of Hepes solution containing 30 mM KCl. Force was measured with a strain gauge, membrane potential with a microelectrode, and [Ca2+]i with fura-2 and a CCD camera in the presence or absence of the 30 mM KCl jet (24°C, [Ca2+]o = 3.0 mM). Arrhythmogenic Ca2+ waves were induced by 2.5-Hz stimulus trains for 7.5 s.
Results: The 30 mM KCl jet increased the velocity of Ca2+ waves starting from the border zone (BZ) between the KCl jet-exposed region and the other regions in the absence and presence of 100 μM streptomycin (n = 6, P < 0.01), a stretch-activated channel blocker, and occasionally triggered arrhythmias. This 30 mM KCl jet depolarized the resting membrane potential (n = 6, P < 0.01) and shortened the action potential duration at the potential level of −30 mV (n = 6, P < 0.01) inside the exposed region, causing spatial non-uniformity of the membrane potential. This KCl jet caused a systolic decrease (n = 8, P < 0.05) and a diastolic increase in [Ca2+]i (n = 8, P < 0.05) inside the exposed region, resulting in spatial non-uniformity of both [Ca2+]i and contraction. Cilnidipine (10 μM), a L-type Ca2+ channel blocker, and SEA0400 (3 μM), an Na+-Ca2+ exchange blocker, suppressed the KCl jet-induced systolic decrease and diastolic increase in [Ca2+]i, respectively (n = 6), and further suppressed the KCl jet-induced increase in the velocity of Ca2+ wave (n = 6). Importantly, a massive decrease (∼90%) in contraction by 20 mM 2,3-butanedione monoxime (n = 6) or 10 μM blebbistatin, a myosin II ATPase inhibitor (n = 5), suppressed the KCl jet-induced increase in the velocity of Ca2+ waves and decreased the occurrence of arrhythmias.
Conclusions: These results suggest that, under the condition of the regional increase in [K+]o, non-uniformity of muscle contraction plays an important role in the occurrence of arrhythmias by acceleration of Ca2+ waves, probably resulting from Ca2+ dissociated from the myofilaments within the BZ.
- © 2010 by American Heart Association, Inc.