title: Early subcellular Ca2+ remodelling and increased propensity for Ca2+ alternans in left atrial myocytes from hypertensive rats.
abstract: OBJECTIVE
  Hypertension is a major risk factor for atrial fibrillation. We hypothesized that arterial hypertension would alter atrial myocyte calcium (Ca2+) handling and that these alterations would serve to trigger atrial tachyarrhythmias.
  
  
  RESULTS
  Left atria or left atrial (LA) myocytes were isolated from spontaneously hypertensive rats (SHR) or normotensive Wistar-Kyoto (WKY) controls. Early after the onset of hypertension, at 3 months of age, there were no differences in Ca2+ transients (CaTs) or expression and phosphorylation of Ca2+ handling proteins between SHR and WKY. At 7 months of age, when left ventricular (LV) hypertrophy had progressed and markers of fibrosis were increased in left atrium, CaTs (at 1 Hz stimulation) were still unchanged. Subcellular alterations in Ca2+ handling were observed, however, in SHR atrial myocytes including (i) reduced expression of the α1C subunit of and reduced Ca2+ influx through L-type Ca2+ channels, (ii) reduced expression of ryanodine receptors with increased phosphorylation at Ser2808, (iii) decreased activity of the Na+ / Ca2+ exchanger (at unaltered intracellular Na+ concentration), and (iv) increased SR Ca2+ load with reduced fractional release. These changes were associated with an increased propensity of SHR atrial myocytes to develop frequency-dependent, arrhythmogenic Ca2+ alternans.
  
  
  CONCLUSIONS
  In SHR, hypertension induces early subcellular LA myocyte Ca2+ remodelling during compensated LV hypertrophy. In basal conditions, atrial myocyte CaTs are not changed. At increased stimulation frequency, however, SHR atrial myocytes become more prone to arrhythmogenic Ca2+ alternans, suggesting a link between hypertension, atrial Ca2+ homeostasis, and development of atrial tachyarrhythmias.
authors.affiliation: Institute of Pharmacology and Clinical Pharmacy, Biochemical and Pharmacological Center (BPC) Marburg, Philipps-University Marburg, Karl-von-Frisch-Str. 1, 35032 Marburg, Germany.
authors.forename: Florentina
authors.initials: F
authors.lastname: Pluteanu
authors.affiliation: Institute of Pharmacology and Clinical Pharmacy, Biochemical and Pharmacological Center (BPC) Marburg, Philipps-University Marburg, Karl-von-Frisch-Str. 1, 35032 Marburg, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Heß
authors.affiliation: Institute of Pharmacology and Clinical Pharmacy, Biochemical and Pharmacological Center (BPC) Marburg, Philipps-University Marburg, Karl-von-Frisch-Str. 1, 35032 Marburg, Germany.
authors.forename: Jelena
authors.initials: J
authors.lastname: Plackic
authors.affiliation: Institute of Pharmacology and Clinical Pharmacy, Biochemical and Pharmacological Center (BPC) Marburg, Philipps-University Marburg, Karl-von-Frisch-Str. 1, 35032 Marburg, Germany.
authors.forename: Yulia
authors.initials: Y
authors.lastname: Nikonova
authors.affiliation: Institute of Pharmacology and Clinical Pharmacy, Biochemical and Pharmacological Center (BPC) Marburg, Philipps-University Marburg, Karl-von-Frisch-Str. 1, 35032 Marburg, Germany.
authors.forename: Judit
authors.initials: J
authors.lastname: Preisenberger
authors.affiliation: Working Group of Molecular Electrophysiology, Medical Faculty, Otto-von-Guericke-University Magdeburg, Magdeburg, Germany.
authors.forename: Alicja
authors.initials: A
authors.lastname: Bukowska
authors.affiliation: Department of Physiology, Cardiovascular Research Institute Maastricht, University Maastricht, Maastricht, The Netherlands.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Schotten
authors.affiliation: Institute of Physiology, Ruhr-University Bochum, Bochum, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Rinne
authors.affiliation: Institute of Physiology, Ruhr-University Bochum, Bochum, Germany.
authors.forename: Marie-Cecile
authors.initials: MC
authors.lastname: Kienitz
authors.affiliation: Institute of Anatomy and Cell Biology, Philipps-University Marburg, Marburg, Germany.
authors.forename: Martin K-H
authors.initials: MK
authors.lastname: Schäfer
authors.affiliation: Institute of Anatomy and Cell Biology, Philipps-University Marburg, Marburg, Germany.
authors.forename: Eberhard
authors.initials: E
authors.lastname: Weihe
authors.affiliation: Working Group of Molecular Electrophysiology, Medical Faculty, Otto-von-Guericke-University Magdeburg, Magdeburg, Germany St. Vincenz-Hospital, Paderborn, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Goette
authors.affiliation: Institute of Pharmacology and Clinical Pharmacy, Biochemical and Pharmacological Center (BPC) Marburg, Philipps-University Marburg, Karl-von-Frisch-Str. 1, 35032 Marburg, Germany jens.kockskaemper@staff.uni-marburg.de.
authors.forename: Jens
authors.initials: J
authors.lastname: Kockskämper
mesh_terms: D000818:Animals; D001145:Arrhythmias, Cardiac / Q000453:epidemiology* / Q000378:metabolism* / Q000503:physiopathology; D064752:Atrial Remodeling / Q000502:physiology*; D002118:Calcium / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000378:metabolism; D004195:Disease Models, Animal; D006325:Heart Atria / Q000378:metabolism* / Q000473:pathology; D006973:Hypertension / Q000378:metabolism* / Q000473:pathology; D008297:Male; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology; D018408:Patch-Clamp Techniques; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012307:Risk Factors; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D019831:Sodium-Calcium Exchanger / Q000378:metabolism; D013610:Tachycardia / Q000453:epidemiology / Q000378:metabolism / Q000503:physiopathology
chemical_list: D020746:Calcium Channels, L-Type; D019831:Sodium-Calcium Exchanger; D012964:Sodium; D002118:Calcium
keywords: Alternans; Atrium; Calcium; Hypertension