A Model of Canine Purkinje Cell Electrophysiology and Ca2+ Cycling

Purkinje cells (Pcell) are characterized by different electrophysiological properties of Ca2+ cycling processes than ventricular myocytes (V cell) and are frequently involved in ventricular arrhythmias. Yet, the mechanistic basis for their arrhythmic Ca2+ cycling, and their rate dependence; (2) investigate mechanisms underlying Pcell arrhythmogenicity; and compare Pcell and Vcell electrophysiology, Ca2+ cycling, and we developed a new mathematical model of Pcell. The Ca2+ subsystem includes spatial organization and receptors distribution unique to Pcell. Resulsts were (1) in Pcell and Vcell, Na+ accumulation via its augmentation of repolarizing I-NaK, I-NaL contributres additional length (2) steep Pcell restituion is attributable to slow recovery of I-NaL; (3) biphasic Ca2+ transients of Pcell reflect the delay between Ca2+ alternans, unlike heterogeneity of Ca2+ cycling attributable to refractoriness of Ca2+ release from corbular sarcoplasmic reticulum and junctional sarcoplasmic reticulum; (6) greater Pcell vulnerability to delayed afterdepolarizations is attributable to higher sarcoplasmic reticulum Ca2+ content of ionic currents that reduce excitation threshold and promote triggered activity; and (7) early after of I-NaL2 whereas I-CaL plays this role in Vcell. Steeper rate dependence of action potential and Ca2+ transients, central peripheral heterogeneity of Ca2+ cycling, and distinct ion channel profile underlie grater arrhythmic vulnerability of Pcell compared to Vcell. (Circ Res. 2011;109:71-79).