title: Intracellular Ca2+ release underlies the development of phase 2 in mouse ventricular action potentials.
abstract: The ventricular action potential (AP) is characterized by a fast depolarizing phase followed by a repolarization that displays a second upstroke known as phase 2. This phase is generally not present in mouse ventricular myocytes. Thus we performed colocalized electrophysiological and optical recordings of APs in Langendorff-perfused mouse hearts founding a noticeable phase 2. Ryanodine as well as nifedipine reduced phase 2. Our hypothesis is that a depolarizing current activated by Ca(2+) released from the sarcoplasmic reticulum (SR) rather than the "electrogenicity" of the L-type Ca(2+) current is crucial in the generation of mouse ventricular phase 2. When Na(+) was partially replaced by Li(+) in the extracellular perfusate or the organ was cooled down, phase 2 was reduced. These results suggest that the Na(+)/Ca(2+) exchanger functioning in the forward mode is driving the depolarizing current that defines phase 2. Phase 2 appears to be an intrinsic characteristic of single isolated myocytes and not an emergent property of the tissue. As in whole heart experiments, ventricular myocytes impaled with microelectrodes displayed a large phase 2 that significantly increases when temperature was raised from 22 to 37°C. We conclude that mouse ventricular APs display a phase 2; however, changes in Ca(2+) dynamics and thermodynamic parameters also diminish phase 2, mostly by impairing the Na(+)/Ca(2+) exchanger. In summary, these results provide important insights about the role of Ca(2+) release in AP ventricular repolarization under physiological and pathological conditions.
authors.affiliation: Biological Engineering and Small Scale Technologies Program, School of Engineering, University of California, Merced, CA 95343, USA.
authors.forename: Marcela
authors.initials: M
authors.lastname: Ferreiro
authors.forename: Azadé D
authors.initials: AD
authors.lastname: Petrosky
authors.forename: Ariel L
authors.initials: AL
authors.lastname: Escobar
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002478:Cells, Cultured; D008094:Lithium / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000502:physiology*; D009543:Nifedipine / Q000494:pharmacology; D012433:Ryanodine / Q000494:pharmacology; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D019831:Sodium-Calcium Exchanger / Q000502:physiology; D016276:Ventricular Function / Q000187:drug effects / Q000502:physiology*
chemical_list: D002121:Calcium Channel Blockers; D019831:Sodium-Calcium Exchanger; D012433:Ryanodine; D008094:Lithium; D009543:Nifedipine; D002118:Calcium