title: Action potential duration determines sarcoplasmic reticulum Ca2+ reloading in mammalian ventricular myocytes.
abstract: After sarcoplasmic reticulum (SR) Ca2+ depletion in intact ventricular myocytes, electrical activity promotes SR Ca2+ reloading and recovery of twitch amplitude. In ferret, recovery of twitch and caffeine-induced contracture required fewer twitches than in rabbit or rat. In rat, there was no difference in action potential duration at 90% repolarization (APD90) at steady state (SS) versus at the first post-depletion (PD) twitch. The SS APD90 was similar in ferret and rabbit (but longer than in rat). However, compared to SS, the PD APD90 was lengthened in ferret, but shortened in rabbit. When rabbit myocytes were subjected to AP-clamp patterns during SR Ca2+ reloading (ferret- or rabbit-type APs), reloading was much faster using the ferret AP templates. We conclude that the faster SR Ca2+ refilling in ferret is due to the increased Ca2+ influx during the longer PD AP. The PD versus SS APD90 difference was suppressed by thapsigargin in ferret (indicating Ca2+ dependence). In rabbit, the PD AP shortening depended on the preceding diastolic interval (rather than Ca2+), because rest produced the same AP shortening, and SS APD90 increased as a function of frequency (in contrast to ferret). Transient outward current (Ito) was larger and recovered from inactivation much faster in ferret than in rabbit. Moreover, slow Ito recovery (tau approximately 3 s) in rabbit was a much larger fraction of Ito. Our data and a computational model (including two Ito components) suggest that in rabbit the slowly recovering Ito is responsible for short post-rest and PD APs, for the unusual frequency dependence of APD90, and ultimately for the slower post-depletion SR Ca2+ reloading.
authors.affiliation: Centro de Engenharia Biomédica, Universidade Estadual de Campinas, 13084-971 Campinas, SP, Brazil. rosana@ceb.unicamp.br
authors.forename: Rosana A
authors.initials: RA
authors.lastname: Bassani
authors.forename: Julio
authors.initials: J
authors.lastname: Altamirano
authors.forename: José L
authors.initials: JL
authors.lastname: Puglisi
authors.forename: Donald M
authors.initials: DM
authors.lastname: Bers
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D005289:Ferrets; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism*; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism*; D013045:Species Specificity
chemical_list: D002110:Caffeine; D002118:Calcium