title: Comparison of contraction and calcium handling between right and left ventricular myocytes from adult mouse heart: a role for repolarization waveform.
abstract: In the mammalian heart, the right ventricle (RV) has a distinct structural and electrophysiological profile compared to the left ventricle (LV). However, the possibility that myocytes from the RV and LV have different contractile properties has not been established. In this study, sarcomere shortening, [Ca2+]i transients and Ca2+ and K+ currents in unloaded myocytes isolated from the RV, LV epicardium (LVepi) and LV endocardium (LVendo) of adult mice were evaluated. Maximum sarcomere shortening elicited by field stimulation was graded in the order: LVendo > LVepi > RV. Systolic [Ca2+]i was higher in LVendo myocytes than in RV myocytes. Voltage-clamp experiments in which action potential (AP) waveforms from RV and LVendo were used as the command signal, demonstrated that total Ca2+ influx and myocyte shortening were larger in response to the LVendo AP, independent of myocyte subtypes. Evaluation of possible regional differences in myocyte Ca2+ handling was based on: (i) the current-voltage relation of the Ca2+ current; (ii) sarcoplasmic reticulum Ca2+ uptake; and (iii) mRNA expression of important components of the Ca2+ handling system. None of these were significantly different between RV and LVendo. In contrast, the Ca2+-independent K+ current, which modulates AP repolarization, was significantly different between RV, LVepi and LVendo. These results suggest that these differences in K+ currents can alter AP duration and modulate the [Ca2+]i transient and corresponding contraction. In summary, these findings provide an initial description of regional differences in excitation-contraction coupling in the adult mouse heart [corrected]
authors.affiliation: Department of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0412, USA.
authors.forename: Richard P
authors.initials: RP
authors.lastname: Kondo
authors.forename: Dorothy A
authors.initials: DA
authors.lastname: Dederko
authors.forename: Christine
authors.initials: C
authors.lastname: Teutsch
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Chrast
authors.forename: Daniele
authors.initials: D
authors.lastname: Catalucci
authors.forename: Kenneth R
authors.initials: KR
authors.lastname: Chien
authors.forename: Wayne R
authors.initials: WR
authors.lastname: Giles
mesh_terms: D000251:Adenosine Triphosphatases / Q000032:analysis; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000032:analysis / Q000235:genetics; D005786:Gene Expression Regulation; D006352:Heart Ventricles / Q000737:chemistry / Q000166:cytology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009200:Myocardial Contraction / Q000502:physiology*; D032383:Myocytes, Cardiac / Q000737:chemistry / Q000166:cytology / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019837:Ryanodine Receptor Calcium Release Channel / Q000032:analysis / Q000235:genetics; D012518:Sarcomeres / Q000502:physiology / Q000648:ultrastructure; D012519:Sarcoplasmic Reticulum / Q000201:enzymology; D019831:Sodium-Calcium Exchanger / Q000032:analysis / Q000235:genetics; D016276:Ventricular Function
chemical_list: D020746:Calcium Channels, L-Type; C419385:L-type calcium channel alpha(1C); C499849:NCX1 protein, mouse; D012333:RNA, Messenger; D019837:Ryanodine Receptor Calcium Release Channel; D019831:Sodium-Calcium Exchanger; D000251:Adenosine Triphosphatases; D011188:Potassium; D002118:Calcium