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.

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.

Similar to our previous report, highly frequent traveling micro Ca²⁺ transients(μCaiTs) and cell-wide Ca²⁺waves were seen in IZPCs in the absence of any drug. Isoproterenol (ISO) increased μCaiTs 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.

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.