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

In the ischemic myocar dium, 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 Ca ²⁺ ([Ca ²⁺] _i) were measured in rat ventricular trabeculae. A "regional" or "global" increase in [K ⁺] _o was 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 [Ca ²⁺] _i (Ca _cw) during Ca ²+ waves was measured (24°C, 3.0 mmol/l [Ca ²⁺] _o). A regional increase in [K ⁺] _o caused nonuniform [Ca ²⁺] _i and contraction. In the presence of isoproterenol, the regional increase in [K ⁺] _o induced sustained arrhythmias in 10 of 14 trabeculae, whereas the global increase did not induce such arrhythmias. During sustained arrhythmias, Ca ²⁺ surged within the jet-exposed region. In the absence of isoproterenol, the regional increase in [K ⁺] _o increased Ca _cw, whereas the global increase decreased it. This increase in Ca _cw with the regional increase in [K ⁺] _o was 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/l2,3-butanedione monoxime; and 3) 10 μmol/l blebbistatin. A regional but not a global increase in [K ⁺] _o induces sustained arrhythmias, probably due to nonuniform excitation-contraction coupling. The same mechanism may underlie arrhythmias during ischemia.