A Model of Canine Purkinje Cell Electrophysiology and Ca2 Cycling Rate Dependence, Triggered Activity, and Comparison to

Abstract: Purkinje cells (Pcell) are characterized by different electrophysiological properties and Ca2 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, Ca2 cycling, and their rate dependence; (2) investigate mechanisms underlying Pcell arrhythmogenicity; and compare Pcell and Vcell electrophysiology, Ca2 cycling, and arrhythmic properties. We developed a new mathematical model of Pcell. The Ca2 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 Ca2 transients of Pcell reflect the delay between Ca2 release from junctional sarcoplasmic reticulum and corbular sarcoplasmic reticulum; (4) Pcell Ca2 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 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 Ca