title: Potential effects of intrinsic heart pacemaker cell mechanisms on dysrhythmic cardiac action potential firing.
abstract: The heart's regular electrical activity is initiated by specialized cardiac pacemaker cells residing in the sinoatrial node. The rate and rhythm of spontaneous action potential firing of sinoatrial node cells are regulated by stochastic mechanisms that determine the level of coupling of chemical to electrical clocks within cardiac pacemaker cells. This coupled-clock system is modulated by autonomic signaling from the brain via neurotransmitter release from the vagus and sympathetic nerves. Abnormalities in brain-heart clock connections or in any molecular clock activity within pacemaker cells lead to abnormalities in the beating rate and rhythm of the pacemaker tissue that initiates the cardiac impulse. Dysfunction of pacemaker tissue can lead to tachy-brady heart rate alternation or exit block that leads to long atrial pauses and increases susceptibility to other cardiac arrhythmia. Here we review evidence for the idea that disturbances in the intrinsic components of pacemaker cells may be implemented in arrhythmia induction in the heart.
authors.affiliation: Biomedical Engineering Faculty, Technion-Israel Institute of Technology Haifa, Israel.
authors.forename: Yael
authors.initials: Y
authors.lastname: Yaniv
authors.affiliation: Laboratory of Cardiovascular Science, Biomedical Research Center, Intramural Research Program, National Institute on Aging, National Institutes of Health Baltimore, MD, USA.
authors.forename: Kenta
authors.initials: K
authors.lastname: Tsutsui
authors.affiliation: Laboratory of Cardiovascular Science, Biomedical Research Center, Intramural Research Program, National Institute on Aging, National Institutes of Health Baltimore, MD, USA.
authors.forename: Edward G
authors.initials: EG
authors.lastname: Lakatta
keywords: arrhythmias; atrial fibrillation; coupled-clock pacemaker system; heart rate variability; sinus node disease