Cardiac automaticity: basic concepts and clinical observations

Vetulli, Héctor; Elizari, Marcelo V.; Naccarelli, Gerald V.; González, Mario D.

doi:10.1007/s10840-018-0423-2

Cited by 14 publications

(13 citation statements)

References 38 publications

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“…; Vetulli et al . ). At the ventricular myocyte level, positive inotropy is primarily mediated by phosphorylation of L‐type Ca 2+ channels (carrying I CaL ), phospholamban (PLB), and ryanodine receptors (RyRs), which increase the Ca 2+ available for contraction.…”

Section: Introductionmentioning

confidence: 97%

Different paths, same destination: divergent action potential responses produce conserved cardiac fight‐or‐flight response in mouse and rabbit hearts

Wang

Morotti

Tapa

et al. 2019

The Journal of Physiology

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Key pointsr Cardiac electrophysiology and Ca 2+ handling change rapidly during the fight-or-flight response to meet physiological demands.r Despite dramatic differences in cardiac electrophysiology, the cardiac fight-or-flight response is highly conserved across species.r In this study, we performed physiological sympathetic nerve stimulation (SNS) while optically mapping cardiac action potentials and intracellular Ca 2+ transients in innervated mouse and rabbit hearts.r Despite similar heart rate and Ca 2+ handling responses between mouse and rabbit hearts, we found notable species differences in spatio-temporal repolarization dynamics during SNS.r Species-specific computational models revealed that these electrophysiological differences allowed for enhanced Ca 2+ handling (i.e. enhanced inotropy) in each species, suggesting that electrophysiological responses are fine-tuned across species to produce optimal cardiac fight-or-flight responses.Abstract Sympathetic activation of the heart results in positive chronotropy and inotropy, which together rapidly increase cardiac output. The precise mechanisms that produce the electrophysiological and Ca 2+ handling changes underlying chronotropic and inotropic responses have been studied in detail in isolated cardiac myocytes. However, few studies have examined the dynamic effects of physiological sympathetic nerve activation on cardiac action potentials (APs) and intracellular Ca 2+ transients (CaTs) in the intact heart. Here, we performed bilateral sympathetic nerve stimulation (SNS) in fully innervated, Langendorff-perfused rabbit and mouse Dr Lianguo Wang graduated with a medical degree from Tianjin Medical University, China. He has been working as a scientist in North America for over 2 decades with a diverse background in cardiac research, including cardiac arrhythmias and intracellular calcium handling. His current research focuses mainly on cardiac autonomic control in health and disease using ex vivo high-speed, high-resolution optical mapping of transmembrane potential and intracellular calcium in isolated innervated hearts. 3868L. Wang and others J Physiol 597.15 hearts. Dual optical mapping with voltage-and Ca 2+ -sensitive dyes allowed for analysis of spatio-temporal AP and CaT dynamics. The rabbit heart responded to SNS with a monotonic increase in heart rate (HR), monotonic decreases in AP and CaT duration (APD, CaTD), and a monotonic increase in CaT amplitude. The mouse heart had similar HR and CaT responses; however, a pronounced biphasic APD response occurred, with initial prolongation (50.9 ± 5.1 ms at t = 0 s vs. 60.6 ± 4.1 ms at t = 15 s, P < 0.05) followed by shortening (46.5 ± 9.1 ms at t = 60 s, P = NS vs. t = 0). We determined the biphasic APD response in mouse was partly due to dynamic changes in HR during SNS and was exacerbated by β-adrenergic activation. Simulations with species-specific cardiac models revealed that transient APD prolongation in mouse allowed for greater and more rapid CaT responses, suggesting more rapid increases in cont...

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Section: Introductionmentioning

confidence: 97%

Different paths, same destination: divergent action potential responses produce conserved cardiac fight‐or‐flight response in mouse and rabbit hearts

Wang

Morotti

Tapa

et al. 2019

The Journal of Physiology

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“…Nonetheless, the significant similarities in the electrophysiological and biophysical properties of I Kr in mammalian SAN suggests that our results need to be seriously considered when seeking to understand or fully explain the ionic basis of the mammalian SAN pacemaker depolarization. Improved functional insights yielded by basic science experiments and clinical investigations will continue to form the basis of contemporary reviews and teaching documents [ 87 ] concerning the genesis of spontaneous pacemaker activity and action potentials in mammalian hearts.…”

Section: Discussionmentioning

confidence: 99%

Physiological Roles of the Rapidly Activated Delayed Rectifier K+ Current in Adult Mouse Heart Primary Pacemaker Activity

Wei

Clark

Giles

et al. 2021

IJMS

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Robust, spontaneous pacemaker activity originating in the sinoatrial node (SAN) of the heart is essential for cardiovascular function. Anatomical, electrophysiological, and molecular methods as well as mathematical modeling approaches have quite thoroughly characterized the transmembrane fluxes of Na+, K+ and Ca2+ that produce SAN action potentials (AP) and ‘pacemaker depolarizations’ in a number of different in vitro adult mammalian heart preparations. Possible ionic mechanisms that are responsible for SAN primary pacemaker activity are described in terms of: (i) a Ca2+-regulated mechanism based on a requirement for phasic release of Ca2+ from intracellular stores and activation of an inward current-mediated by Na+/Ca2+ exchange; (ii) time- and voltage-dependent activation of Na+ or Ca2+ currents, as well as a cyclic nucleotide-activated current, If; and/or (iii) a combination of (i) and (ii). Electrophysiological studies of single spontaneously active SAN myocytes in both adult mouse and rabbit hearts consistently reveal significant expression of a rapidly activating time- and voltage-dependent K+ current, often denoted IKr, that is selectively expressed in the leading or primary pacemaker region of the adult mouse SAN. The main goal of the present study was to examine by combined experimental and simulation approaches the functional or physiological roles of this K+ current in the pacemaker activity. Our patch clamp data of mouse SAN myocytes on the effects of a pharmacological blocker, E4031, revealed that a rapidly activating K+ current is essential for action potential (AP) repolarization, and its deactivation during the pacemaker potential contributes a small but significant component to the pacemaker depolarization. Mathematical simulations using a murine SAN AP model confirm that well known biophysical properties of a delayed rectifier K+ current can contribute to its role in generating spontaneous myogenic activity.

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“…The basis of arrhythmogenesis includes changes in myocardial automaticity, triggered activity, and reentrant mechanisms [33]. Abnormal automaticity refers to the formation of cardiac impulses in normally quiescent cardiac cells and is controlled by multiple factors, including sympathetic and parasympathetic tone, acid-base status, and electrolyte disturbances at the membrane and sub-membrane levels [34]. OSA causes repetitive, cyclical changes in sympathetic tone.…”

Section: Guilt By Association or Public Enemy Number One? Obstructive Sleep Apnea And Cardiac Arrhythmogenesismentioning

confidence: 99%

Obstructive Sleep Apnea and Cardiac Arrhythmias: A Contemporary Review

Laczay

Faulx

2021

JCM

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Obstructive sleep apnea (OSA) is a highly prevalent disorder with a growing incidence worldwide that closely mirrors the global obesity epidemic. OSA is associated with enormous healthcare costs in addition to significant morbidity and mortality. Much of the morbidity and mortality related to OSA can be attributed to an increased burden of cardiovascular disease, including cardiac rhythm disorders. Awareness of the relationship between OSA and rhythm disorders is variable among physicians, a fact that can influence patient care, since the presence of OSA can influence the incidence, prevalence, and successful treatment of multiple rhythm disorders. Herein, we provide a review of this topic that is intentionally broad in scope, covering the relationship between OSA and rhythm disorders from epidemiology and pathophysiology to diagnosis and management, with a particular focus on the recognition of undiagnosed OSA in the general clinical population and the intimate relationship between OSA and atrial fibrillation.

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Cardiac automaticity: basic concepts and clinical observations

Cited by 14 publications

References 38 publications

Different paths, same destination: divergent action potential responses produce conserved cardiac fight‐or‐flight response in mouse and rabbit hearts

Different paths, same destination: divergent action potential responses produce conserved cardiac fight‐or‐flight response in mouse and rabbit hearts

Physiological Roles of the Rapidly Activated Delayed Rectifier K+ Current in Adult Mouse Heart Primary Pacemaker Activity

Obstructive Sleep Apnea and Cardiac Arrhythmias: A Contemporary Review

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