2APB- and JTV519(K201)-sensitive micro Ca2+ waves in arrhythmogenic Purkinje cells that survive in infarcted canine heart

OBJECTIVES/BACKGROUND Studies from several laboratories have implicated intracellular Ca2+ dynamics in the modulation of electrical activity. We have reported that abnormal Ca2+ wave activity is the underlying cause of afterdepolarization-induced electrical activity in subendocardial Purkinje cells that survive in the 48-hour infarcted canine heart. These cells form the focus of arrhythmias at this time postcoronary artery occlusion. METHODS We studied the effects of agonists and antagonists on the abnormal Ca2+ release activity of Purkinje cell aggregates dispersed from the subendocardium 48 hours postcoronary artery occlusion (IZPCs). Studies were completed using epifluorescent microscopy of Fluo-3 loaded Purkinje cells. RESULTS Similar to our previous report, highly frequent traveling micro Ca2+ transients(muCaiTs) and cell-wide Ca2+ waves were seen in IZPCs in the absence of any drug. Isoproterenol (ISO) increased muCaiTs and cell-wide Ca2+ waves in Purkinje cells dispersed from the normal heart (NZPCs). In IZPCs, ISO increased cell-wide wave frequency but had no effect on the already highly frequent micro Ca2+ wave transient activity, suggesting that ISO lowers the threshold of cell-wide generators responding to micro Ca2+ transients. Drugs that block inward sodium or calcium currents (verapamil, tetrodotoxin) had no effect on Ca2+ activity in Purkinje cells. Antagonists of intracellular Ca2+ release channels [ryanodine, JTV519(K201)] greatly suppressed spontaneous Ca2+ release events in IZPCs. 2APB, an agent that blocks IP3 receptors, greatly reduced the frequency of Ca2+ events in IZPCs. CONCLUSIONS In arrhythmogenic Purkinje cells that survive in the infarcted heart, agents that block or inhibit intracellular Ca2+ release channel activity reduced Ca2+ waves and could be antiarrhythmic. (C) 2004 Heart Rhythm Society. All rights reserved.