A Model of Canine Purkinje Cell Electrophysiology and Ca Cycling Rate Dependence, Triggered Activity, and Comparison to Ventricular Myocytes

Purkinje cells (Pcell) are characterized by different electrophysiological properties and Ca cycling processes than ventricular myocytes (Vcell) and are frequently involved in ventricular arrhythmias. Yet, the mechanistic basis for their arrhythmic vulnerability is not completely understood. The objectives were to: (1) characterize Pcell electrophysiology, Ca cycling, and their rate dependence; (2) investigate mechanisms underlying Pcell arrhythmogenicity; and compare Pcell and Vcell electrophysiology, Ca cycling, and arrhythmic properties. We developed a new mathematical model of Pcell. The Ca subsystem includes spatial organization and receptors distribution unique to Pcell. Results were: (1) in Pcell and Vcell, Na accumulation via its augmentation of repolarizing INaK dominates action potential duration adaptation and, in Pcell, INaL contributes additional action potential duration shortening at short cycle length; (2) steep Pcell restitution is attributable to slow recovery of INaL; (3) biphasic Ca 2 transients of Pcell reflect the delay between Ca release from junctional sarcoplasmic reticulum and corbular sarcoplasmic reticulum; (4) Pcell Ca alternans, unlike Vcell, can develop without inducing action potential alternans; (5) Pcell action potential alternans develops at a shorter cycle length than Vcell, with increased subcellular heterogeneity of Ca cycling attributable to refractoriness of Ca release from corbular sarcoplasmic reticulum and junctional sarcoplasmic reticulum; (6) greater Pcell vulnerability to delayed afterdepolarizations is attributable to higher sarcoplasmic reticulum Ca content and ionic currents that reduce excitation threshold and promote triggered activity; and (7) early after depolarizations generation in Pcell is mostly attributable to reactivation of INaL2, whereas ICaL plays this role in Vcell. Steeper rate dependence of action potential and Ca transients, central peripheral heterogeneity of Ca cycling, and distinct ion channel profile underlie greater arrhythmic vulnerability of Pcell compared to Vcell. (Circ Res. 2011;109:71-79.)