k201-compound and 2-aminoethoxydiphenyl-borate

Studies from several laboratories have implicated intracellular Ca(2+) dynamics in the modulation of electrical activity. We have reported that abnormal Ca(2+) 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 Ca(2+) 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 Ca(2+) transients (muCaiTs) and cell-wide Ca(2+) waves were seen in IZPCs in the absence of any drug. Isoproterenol (ISO) increased muCaiTs and cell-wide Ca(2+) 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 Ca(2+) wave transient activity, suggesting that ISO lowers the threshold of cell-wide generators responding to micro Ca(2+) transients. Drugs that block inward sodium or calcium currents (verapamil, tetrodotoxin) had no effect on Ca(2+) activity in Purkinje cells. Antagonists of intracellular Ca(2+) release channels [ryanodine, JTV519(K201)] greatly suppressed spontaneous Ca(2+) release events in IZPCs. 2APB, an agent that blocks IP(3) receptors, greatly reduced the frequency of Ca(2+) events in IZPCs.. In arrhythmogenic Purkinje cells that survive in the infarcted heart, agents that block or inhibit intracellular Ca(2+) release channel activity reduced Ca(2+) waves and could be antiarrhythmic.

Topics: Adrenergic beta-Agonists; Aniline Compounds; Animals; Boron Compounds; Calcium; Calcium Channel Blockers; Calcium Channels; Coloring Agents; Dogs; Isoproterenol; Male; Microscopy, Fluorescence; Myocardial Infarction; Purkinje Cells; Thiazepines; Verapamil; Xanthenes