Background: Extracellular potassium ([K+]o) increases to >20 mM in the ischemic myocardium. We investigated whether this regional increase in [K+]o affects arrhythmias. Methods: To produce a, regional, increase in [K+]o (KR), rat trabeculae were regionally exposed to a jet of solution containing 30 mM KCl. To produce a global, increase in [K+]o (KG), trabeculae were superfused with a solution containing 30 mM KCl. Force, sarcomere length, membrane potential, and [Ca2+]i were measured (24°C, [Ca2+]o=3.0 mM). The velocity (Vprop) and amplitude (CaCW) of Ca2+ waves were measured. Results: KR caused nonuniform contraction and increased the Vprop and Cacw, while KG decreased the Cacw. The increase in the Cacw with KR was not suppressed by 100 μM streptomycin, while it was suppressed by 1) both 10 μM cilnidipine and 3 μM SEA0400, 2) 20 mM 2,3-butanedione monoxime, and 3) 10 μM blebbistatin. With 200 nM isoproterenol, KR induced sustained arrhythmias (>10 s), while KG induced no sustained arrhythmias. During sustained arrhythmias with KR, Ca2+ surged within the border zone (BZ) around the jet-exposed region and were succeeded by synchronous increases in [Ca2+]i. Stoppage of the jet caused the Ca2+ surge to become unclear and resulted in the arrest of sustained arrhythmias. Conclusions: A regional but not global increase in [K+]o induces sustained arrhythmias, probably due to nonuniform contraction.