Evidence map›Paper›PMID 41711620›Full record

ArticleJACC. Clinical electrophysiology2026

Caveolar Compartmentalization of Pacemaker Signaling Ensures Stable Sinoatrial Rhythmicity Which Is Disrupted in Heart Failure.

Di Lang, Haibo Ni, Roman Y Medvedev, Fang Liu, Claudia P Alvarez-Baron, Leonid Tyan, Daniel G P Turner, Aleah Warden, Stefano Morotti, Thomas A Schrauth and 5 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in JACC. Clinical electrophysiology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Article
  2. Downregulation of L-type CaHeart rhythm · 2026
    Article
  3. Article
  4. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors.

Di LangDepartment of Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA; Department of Medicine, University of California-San Francisco, San Francisco, California, USA. Electronic address: di.lang@ucsf.edu.
Haibo NiDepartment of Pharmacology, University of California-Davis, Davis, California, USA; The Medical School, Nanjing University, Nanjing, China.
Roman Y MedvedevDepartment of Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Fang LiuDepartment of Neuroscience, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Claudia P Alvarez-BaronDepartment of Neuroscience, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Leonid TyanDepartment of Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Daniel G P TurnerDepartment of Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Aleah WardenDepartment of Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Stefano MorottiDepartment of Pharmacology, University of California-Davis, Davis, California, USA.
Thomas A SchrauthDepartment of Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Baron ChandaDepartment of Anesthesiology, Washington University in St Louis, St Louis, Missouri, USA.
Timothy J KampDepartment of Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Gail A RobertsonDepartment of Neuroscience, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Eleonora GrandiDepartment of Pharmacology, University of California-Davis, Davis, California, USA.
Alexey V GlukhovDepartment of Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA. Electronic address: aglukhov@medicine.wisc.edu.

Funding

Project 3 (Mercola)P01HL141084 · NHLBI · STANFORD UNIVERSITY · PI MARK MERCOLA · 2019 to 2026
$21.1M
Training Program in Translational Cardiovascular Science (TPTCS)T32HL007936 · NHLBI · UNIVERSITY OF WISCONSIN-MADISON · PI Lee Lochbaum Eckhardt, Gail A Robertson · 2001 to 2026
$11.6M
Biophysical mechanisms of gating and modulation in voltage-gated ion channel superfamilyR35NS116850 · NINDS · WASHINGTON UNIVERSITY · PI Baron Chanda · 2020 to 2026
$6.9M
Training Program In Molecular AND Cellular PharmacologyT32GM008688 · NIGMS · UNIVERSITY OF WISCONSIN-MADISON · PI AUDHYA, ANJON · 1998 to 2020
$6.0M
Translational Control of Cardiac ExcitabilityR01HL131403 · NHLBI · UNIVERSITY OF WISCONSIN-MADISON · PI Gail A Robertson · 2016 to 2026
$6.0M
Development of the Predictive NeuroCardiovascular SimulatorOT2OD026580 · OD · UNIVERSITY OF CALIFORNIA AT DAVIS · PI CLANCY, COLLEEN E, GRANDI, ELEONORA · 2018 to 2021
$5.7M
Sex-specific arrhythmogenic mechanisms of atrial fibrillationR01HL131517 · NHLBI · UNIVERSITY OF CALIFORNIA AT DAVIS · PI Eleonora Grandi · 2016 to 2026
$5.0M
Functional Microdomains in the Heart's Pacemaker: A New Dimension of Cardiac RemodelingR01HL141214 · NHLBI · UNIVERSITY OF WISCONSIN-MADISON · PI Alexey V Glukhov · 2018 to 2026
$3.8M
Caveolae and L-type Calcium Channels in CardiomyocytesR01HL078878 · NHLBI · UNIVERSITY OF WISCONSIN-MADISON · PI BALIJEPALLI, RAVI CHANDRA, KAMP, TIMOTHY J. · 2007 to 2016
$3.1M
Multiomics and Functional Characterization Establish Druggable Targets for PVC-Driven Idiopathic VFR01HL170521 · NHLBI · UNIVERSITY OF WISCONSIN-MADISON · PI Lee Lochbaum Eckhardt, Eleonora Grandi · 2023 to 2026
$3.1M
KCNJ2-Induced Arrhythmia Mechanisms in CPVT and Heart Failure.R01HL139738 · NHLBI · UNIVERSITY OF WISCONSIN-MADISON · PI ECKHARDT, LEE LOCHBAUM · 2018 to 2021
$1.5M
Neutral sphingomyelinase in the mechanical regulation of the heartR01HL182084 · NHLBI · UNIVERSITY OF WISCONSIN-MADISON · PI Lee Lochbaum Eckhardt, Alexey V Glukhov · 2025 to 2026
$1.2M
NHLBI NIH HHS P01 HL141084NHLBI NIH HHS R00 HL138160NHLBI NIH HHS R01 HL078878NHLBI NIH HHS R01 HL131403NHLBI NIH HHS R01 HL131517NHLBI NIH HHS R01 HL139738NHLBI NIH HHS R01 HL141214NHLBI NIH HHS R01 HL170521NHLBI NIH HHS R01 HL173344NHLBI NIH HHS R01 HL182084NHLBI NIH HHS T32 HL007936NIGMS NIH HHS T32 GM008688NIH HHS OT2 OD026580NINDS NIH HHS R35 NS116850
6 · The paper itself

Abstract

backgroundCaveolae are nanoscale, plasma membrane invaginations that compartmentalize ion channels and transporters, including those involved in sinoatrial node (SAN) activity. However, role of caveolae in cardiac pacemaking remains unknown.

objectivesThis study sought to determine the role of caveolae in SAN pacemaking and sinus node dysfunction (SND).

methodsIn vivo electrocardiography, ex vivo optical mapping, in vitro Ca

resultsIn both mouse and human SANs, caveolae compartmentalized HCN4, Ca

conclusionsSAN pacemaking is driven by complex protein interactions within a nanoscale caveolar pacemaker signalosome. Disruption of caveolae leads to SND, demonstrating a new dimension of SAN remodeling and revealing a novel therapeutic target.

Indexed as

Biological ClocksCaveolaeHeart FailureSinoatrial NodeAnimalsCalcium Channels, L-TypeCaveolin 3HumansHyperpolarization-Activated Cyclic Nucleotide-Gated ChannelsMiceMice, KnockoutSodium-Calcium ExchangerCalcium Channels, L-TypeCaveolin 3Hcn4 protein, mouseHyperpolarization-Activated Cyclic Nucleotide-Gated ChannelsSodium-Calcium Exchangercalcium signalingCav3caveolaeheart failuremathematical modelingsinus nodesinus node dysfunction

Identifiers

PMID41711620
PMCPMC12974990

What Socratic holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.