Nonuniform Ca2+ transients in arrhythmogenic Purkinje cells that survive in the infarcted canine heart

Objective and methods: In this Study, we investigated whether Ca2+ transients are altered in Purkinje cell aggregates dispersed front the subendocardium overlying the infarcted zone of the left ventricle (IZPCs) 48 h after coronary artery occlusion. To do so, we combined epifluorescent imaging with microelectrode recordings of IZPCs and normal canine Purkinje cell aggregates (NZPCs). Results: NZPCs respond to an action potential (AP) by a small Ca2+ transient at the cell Surface immediately after the AP upstroke followed by a large [Ca2+] transient, which propagates to the cell core. In addition, focal Ca2+ waves can originate spontaneously later during the AP or during the diastolic interval (Circ Res 2000;86:448-55) and then propagate throughout the aggregate as 'cell-wide Ca2+ waves'. Electrically-evoked Ca2+ transients in IZPCs arose significantly faster than those in NZPCs, and showed substantial spatiotemporal nonuniformity within an IZPC aggregate as well as between IZPC aggregates. IZPCs showed, hitherto undetected, low amplitude, micro Ca2+ transients (extent less than or equal to5 mum) at a fivefold higher incidence than in NZPCs. Micro Ca2+ transients appeared to meander over distances less than or equal to100 mum and reduced the local Ca2+ transient of the next paced beat. Micro Ca2+ transients nearly always preceded the cell-wide Ca2+ waves, which occurred more frequently in IZPCs than in NZPCs and caused non-driven electrical activity of the Purkinje aggregate. Conclusions: Micro Ca2+ transients preceded cell-wide Ca2+ waves so often that it is probable that micro Ca2+ transients induced cell-wide Ca2+ waves. Cell-wide Ca2+ waves, in turn, clearly elicited spontaneous APs. We propose that the high incidence of micro Ca2+ transients in IZPCs is a fundamental element of the abnormal Ca2+ handling of diseased Purkinje cells, underlying arrhythmias originating in the subendocardial Purkinje network post myocardial infarction. (C) 2003 European Society of Cardiology. Published by Elsevier Science B.V. All rights reserved.