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

Masahito Miura, Taiki Hattori, Naomi Murai, Tsuyoshi Nagano, Taichi Nishio, Penelope A. Boyden, Chiyohiko Shindoh

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)H2301-H2309
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume302
Issue number11
DOIs
Publication statusPublished - 2012 Jun 1

Keywords

  • Calcium
  • Calcium waves
  • High extracellular potassium
  • Ischemia

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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