Regional increase in extracellular potassium can be arrhythmogenic due to nonuniform muscle contraction in rat ventricular muscle

Abstract

In the ischemic myocardium, extracellular potassium ([K+]o) increases to ≥20 mmol/l. To determine how lethal arrhythmias occur during ischemia, we investigated whether the increased spatial pattern of [K+]o, i.e., a regional or a global increase, affects the incidence of arrhythmias. Force, sarcomere length, membrane potential, and nonuniform intracellular Ca2+([Ca2+]i) were measured in rat ventricular trabeculae. A “regional” or “global” increase in [K+]owas produced by exposing a restricted region of muscle to a jet of 30 mmol/l KCl or by superfusing trabeculae with a solution containing 30 mmol/l KCl, respectively. The increase in [Ca2+]i(CaCW) during Ca2+waves was measured (24°C, 3.0 mmol/l [Ca2+]o). A regional increase in [K+]ocaused nonuniform [Ca2+]iand contraction. In the presence of isoproterenol, the regional increase in [K+]oinduced sustained arrhythmias in 10 of 14 trabeculae, whereas the global increase did not induce such arrhythmias. During sustained arrhythmias, Ca2+surged within the jet-exposed region. In the absence of isoproterenol, the regional increase in [K+]oincreased CaCW, whereas the global increase decreased it. This increase in CaCWwith the regional increase in [K+]owas not suppressed by 100 μmol/l streptomycin, whereas it was suppressed by 1) a combination of 10 μmol/l cilnidipine and 3 μmol/l SEA0400; 2) 20 mmol/l 2,3-butanedione monoxime; and 3) 10 μmol/l blebbistatin. A regional but not a global increase in [K+]oinduces sustained arrhythmias, probably due to nonuniform excitation-contraction coupling. The same mechanism may underlie arrhythmias during ischemia.