title: 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 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/l 2,3-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.
authors.affiliation: Department of Clinical Physiology, Health Science, Tohoku University Graduate School of Medicine, Sendai, Japan. mmiura@med.tohoku.ac.jp
authors.forename: Masahito
authors.initials: M
authors.lastname: Miura
authors.forename: Taiki
authors.initials: T
authors.lastname: Hattori
authors.forename: Naomi
authors.initials: N
authors.lastname: Murai
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Nagano
authors.forename: Taichi
authors.initials: T
authors.lastname: Nishio
authors.forename: Penelope A
authors.initials: PA
authors.lastname: Boyden
authors.forename: Chiyohiko
authors.initials: C
authors.lastname: Shindoh
mesh_terms: D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced* / Q000503:physiopathology*; D002118:Calcium / Q000378:metabolism; D002316:Cardiotonic Agents / Q000494:pharmacology; D056966:Excitation Contraction Coupling / Q000502:physiology; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D007545:Isoproterenol / Q000494:pharmacology; D008564:Membrane Potentials / Q000502:physiology; D023421:Models, Animal; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology*; D017202:Myocardial Ischemia / Q000378:metabolism / Q000503:physiopathology; D011188:Potassium / Q000009:adverse effects* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D002316:Cardiotonic Agents; D007545:Isoproterenol; D011188:Potassium; D002118:Calcium