title: A model of canine purkinje cell electrophysiology and Ca(2+) cycling: rate dependence, triggered activity, and comparison to ventricular myocytes.
abstract: Purkinje cells (Pcell) are characterized by different electrophysiological properties and Ca(2+) 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(2+) cycling, and their rate dependence; (2) investigate mechanisms underlying Pcell arrhythmogenicity; and compare Pcell and Vcell electrophysiology, Ca(2+) cycling, and arrhythmic properties. We developed a new mathematical model of Pcell. The Ca(2+) subsystem includes spatial organization and receptors distribution unique to Pcell. Results were: (1) in Pcell and Vcell, Na(+) accumulation via its augmentation of repolarizing I(NaK) dominates action potential duration adaptation and, in Pcell, I(NaL) contributes additional action potential duration shortening at short cycle length; (2) steep Pcell restitution is attributable to slow recovery of I(NaL); (3) biphasic Ca(2+) transients of Pcell reflect the delay between Ca(2+) release from junctional sarcoplasmic reticulum and corbular sarcoplasmic reticulum; (4) Pcell Ca(2+) 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(2+) cycling attributable to refractoriness of Ca(2+) release from corbular sarcoplasmic reticulum and junctional sarcoplasmic reticulum; (6) greater Pcell vulnerability to delayed afterdepolarizations is attributable to higher sarcoplasmic reticulum Ca(2+) 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 I(NaL2), whereas I(CaL) plays this role in Vcell. Steeper rate dependence of action potential and Ca(2+) transients, central peripheral heterogeneity of Ca(2+) cycling, and distinct ion channel profile underlie greater arrhythmic vulnerability of Pcell compared to Vcell.
authors.affiliation: Department of Biomedical Engineering and Cardiac Bioelectricity and Arrhythmia Center, Campus Box 1097, Washington University in St. Louis, 1 Brookings Drive, St. Louis, MO 63112, USA.
authors.forename: Pan
authors.initials: P
authors.lastname: Li
authors.forename: Yoram
authors.initials: Y
authors.lastname: Rudy
mesh_terms: D000200:Action Potentials; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology; D002118:Calcium / Q000378:metabolism*; D004285:Dogs; D006352:Heart Ventricles / Q000166:cytology; D008954:Models, Biological; D032383:Myocytes, Cardiac / Q000502:physiology*; D011690:Purkinje Fibers / Q000502:physiology*; D019837:Ryanodine Receptor Calcium Release Channel / Q000502:physiology; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D012964:Sodium / Q000378:metabolism
chemical_list: D019837:Ryanodine Receptor Calcium Release Channel; D012964:Sodium; D002118:Calcium