ArticleFrontiers in physiology2016
Ca(2+)-Clock-Dependent Pacemaking in the Sinus Node Is Impaired in Mice with a Cardiac Specific Reduction in SERCA2 Abundance.
Article in Frontiers in physiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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11 citing papers in PubMed, 24 citations in OpenAlex.
- Electrical stimulation of the dorsal motor nucleus of the vagus in male mice can regulate inflammation without affecting the heart rate.Brain, behavior, and immunity · 2024Article
- Depressed HCN4 function in the type 2 diabetic sinoatrial node.Molecular and cellular biochemistry · 2023Article
- Sinus node dysfunction: current understanding and future directions.American journal of physiology. Heart and circulatory physiology · 2023Review
- Heart failure in mice induces a dysfunction of the sinus node associated with reduced CaMKII signaling.The Journal of general physiology · 2022Article
- Editorial: Vascular Disease Multi-Scale Multi-Physics Modeling and Experimental Data.Frontiers in physiology · 2022Article
- Synergistic and Attenuating Effect of Electroacupuncture on Aconitine in Improving Heart Failure and Its Calcium Regulation Mechanism.Evidence-based complementary and alternative medicine : eCAM · 2022Article
- Remodeling of the Purkinje Network in Congestive Heart Failure in the Rabbit.Circulation. Heart failure · 2021Article
- Sinus node-like pacemaker mechanisms regulate ectopic pacemaker activity in the adult rat atrioventricular ring.Scientific reports · 2019Article
- Quantitative proteomics and single-nucleus transcriptomics of the sinus node elucidates the foundation of cardiac pacemaking.Nature communications · 2019Article
- Functional Microdomains in Heart's Pacemaker: A Step Beyond Classical Electrophysiology and Remodeling.Frontiers in physiology · 2018Review
- Gene Expressions Underlying Mishandled Calcium Clearance and Elevated Generation of Reactive Oxygen Species in the Coronary Artery Smooth Muscle Cells of Chronic Heart Failure Rats.Chinese medical journal · 2017Article
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe sarcoplasmic reticulum Ca(2+)-ATPase (SERCA2) pump is an important component of the Ca(2+)-clock pacemaker mechanism that provides robustness and flexibility to sinus node pacemaking. We have developed transgenic mice with reduced cardiac SERCA2 abundance (Serca2 KO) as a model for investigating SERCA2's role in sinus node pacemaking. METHODS AND
resultsIn Serca2 KO mice, ventricular SERCA2a protein content measured by Western blotting was 75% (P < 0.05) lower than that in control mice (Serca2 FF) tissue. Immunofluorescent labeling of SERCA2a in ventricular, atrial, sinus node periphery and center tissue sections revealed 46, 45, 55, and 34% (all P < 0.05 vs. Serca2 FF) lower labeling, respectively and a mosaic pattern of expression. With telemetric ECG surveillance, we observed no difference in basal heart rate, but the PR-interval was prolonged in Serca2 KO mice: 49 ± 1 vs. 40 ± 1 ms (P < 0.001) in Serca2 FF. During exercise, heart rate in Serca2 KO mice was elevated to 667 ± 22 bpm, considerably less than 780 ± 17 bpm (P < 0.01) in Serca2 FF. In isolated sinus node preparations, 2 mM Cs(+) caused bradycardia that was equally pronounced in Serca2 KO and Serca2 FF (32 ± 4% vs. 29 ± 5%), indicating no change in the pacemaker current, I f. Disabling the Ca(2+)-clock with 2 μM ryanodine induced bradycardia that was less pronounced in Serca2 KO preparations (9 ± 1% vs. 20 ± 3% in Serca2 FF; P < 0.05), suggesting a disrupted Ca(2+)-clock. Mathematical modeling was used to dissect the effects of membrane- and Ca(2+)-clock components on Serca2 KO mouse heart rate and sinus node action potential. Computer modeling predicted a slowing of heart rate with SERCA2 downregulation and the heart rate slowing was pronounced at >70% reduction in SERCA2 activity.
conclusionsSerca2 KO mice show a disrupted Ca(2+)-clock-dependent pacemaker mechanism contributing to impaired sinus node and atrioventricular node function.
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