OBJECTIVES: The purpose of the study was to characterize the ionic and molecular mechanisms in the very early phases of electrical remodeling in a rabbit model of rapid atrial pacing (RAP). BACKGROUND: Long-term atrial fibrillation reduces L-type Ca(2+) (I(Ca,L)) and transient outward K(+) (I(to)) currents by transcriptional downregulation of the underlying ionic channels. However, electrical remodeling starts early after the onset of rapid atrial rates. The time course of ion current and channel modulation in these early phases of remodeling is currently unknown. METHODS: Rapid (600 beats/min) right atrial pacing was performed in rabbits. Animals were divided into five groups with pacing durations between 0 and 96 h. Ionic currents were measured by patch clamp techniques; messenger ribonucleic acid (mRNA) and protein expression were measured by reverse transcription-polymerase chain reaction and Western blot, respectively. RESULTS: L-type calcium current started to be reduced (by 47%) after 12 h of RAP and continued to decline as pacing continued. Current changes were preceded or paralleled by decreased mRNA expression of the Ca(2+) channel beta subunits CaB2a, CaB2b, and CaB3, whereas significant reductions in the alpha(1) subunit mRNA and protein expression began 24 h after pacing onset. Transient outward potassium current densities were not altered within the first 12 h, but after 24 h, currents were reduced by 48%. Longer pacing periods did not further decrease I(to). Current changes were paralleled by reduced Kv4.3 mRNA expression. Kv4.2, Kv1.4, and the auxiliary subunit KChIP2 were not affected. CONCLUSIONS: L-type calcium current and I(to) are reduced in early phases of electrical remodeling. A major mechanism appears to be transcriptional downregulation of underlying ion channels, which partially preceded ion current changes.
OBJECTIVES: The purpose of the study was to characterize the ionic and molecular mechanisms in the very early phases of electrical remodeling in a rabbit model of rapid atrial pacing (RAP). BACKGROUND: Long-term atrial fibrillation reduces L-type Ca(2+) (I(Ca,L)) and transient outward K(+) (I(to)) currents by transcriptional downregulation of the underlying ionic channels. However, electrical remodeling starts early after the onset of rapid atrial rates. The time course of ion current and channel modulation in these early phases of remodeling is currently unknown. METHODS: Rapid (600 beats/min) right atrial pacing was performed in rabbits. Animals were divided into five groups with pacing durations between 0 and 96 h. Ionic currents were measured by patch clamp techniques; messenger ribonucleic acid (mRNA) and protein expression were measured by reverse transcription-polymerase chain reaction and Western blot, respectively. RESULTS: L-type calcium current started to be reduced (by 47%) after 12 h of RAP and continued to decline as pacing continued. Current changes were preceded or paralleled by decreased mRNA expression of the Ca(2+) channel beta subunits CaB2a, CaB2b, and CaB3, whereas significant reductions in the alpha(1) subunit mRNA and protein expression began 24 h after pacing onset. Transient outward potassium current densities were not altered within the first 12 h, but after 24 h, currents were reduced by 48%. Longer pacing periods did not further decrease I(to). Current changes were paralleled by reduced Kv4.3 mRNA expression. Kv4.2, Kv1.4, and the auxiliary subunit KChIP2 were not affected. CONCLUSIONS: L-type calcium current and I(to) are reduced in early phases of electrical remodeling. A major mechanism appears to be transcriptional downregulation of underlying ion channels, which partially preceded ion current changes.
Authors: Roman Laszlo; Christoph Winkler; Stefan Wöhrl; Ralf E Wessel; Sara Laszlo; Mathias C Busch; Jürgen Schreieck; Ralph F Bosch Journal: Naunyn Schmiedebergs Arch Pharmacol Date: 2007-09-15 Impact factor: 3.000
Authors: Roman Laszlo; Christoph Winkler; Stefan Wöhrl; Sara Laszlo; Christian Eick; Jürgen Schreieck; Ralph F Bosch Journal: Exp Clin Cardiol Date: 2007
Authors: Hassan Musa; Kuljeet Kaur; Ryan O'Connell; Matt Klos; Guadalupe Guerrero-Serna; Uma Mahesh R Avula; Todd J Herron; Jerômé Kalifa; Justus M B Anumonwo; José Jalife Journal: Heart Rhythm Date: 2013-03-14 Impact factor: 6.343
Authors: Raphael P Martins; Kuljeet Kaur; Elliot Hwang; Rafael J Ramirez; B Cicero Willis; David Filgueiras-Rama; Steven R Ennis; Yoshio Takemoto; Daniela Ponce-Balbuena; Manuel Zarzoso; Ryan P O'Connell; Hassan Musa; Guadalupe Guerrero-Serna; Uma Mahesh R Avula; Michael F Swartz; Sandesh Bhushal; Makarand Deo; Sandeep V Pandit; Omer Berenfeld; José Jalife Journal: Circulation Date: 2014-01-24 Impact factor: 29.690