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.
|Journal||American Journal of Physiology - Heart and Circulatory Physiology|
|Publication status||Published - 2012 Jun 1|
- Calcium waves
- High extracellular potassium
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine
- Physiology (medical)