ArticleJournal of molecular and cellular cardiology2009
Functional role of CLC-2 chloride inward rectifier channels in cardiac sinoatrial nodal pacemaker cells.
Article in Journal of molecular and cellular cardiology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
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Who cites it
29 citing papers in PubMed, 1 synthesis or guideline pooled it, 42 citations in OpenAlex.
- A meta-analysis of acupuncture use in the treatment of cognitive impairment after stroke.Journal of alternative and complementary medicine (New York, N.Y.) · 2014Pooled it
- Aging and sinus node dysfunction: mechanisms and future directions.Clinical science (London, England : 1979) · 2025Review
- Association between serum chloride and in-hospital mortality in congestive heart failure with diabetes: Data from the MIMIC-IV database.Journal of diabetes and metabolic disorders · 2024Article
- Adrenal Anion Channels: New Roles in Zona Glomerulosa Physiology and in the Pathophysiology of Primary Aldosteronism.Handbook of experimental pharmacology · 2024Article
- Caveolin-3 prevents swelling-induced membrane damage via regulation of IBiophysical journal · 2022Article
- RNAseq shows an all-pervasive day-night rhythm in the transcriptome of the pacemaker of the heart.Scientific reports · 2021Article
- Electrophysiological and Molecular Mechanisms of Sinoatrial Node Mechanosensitivity.Frontiers in cardiovascular medicine · 2021Article
- Hypochloraemia in Patients with Heart Failure: Causes and Consequences.Cardiology and therapy · 2020Review
- Negative chronotropic and inotropic effects of lubiprostone on iPS cell-derived cardiomyocytes via activation of CFTR.BMC complementary medicine and therapies · 2020Article
- A Novel Loss-of-Function Variant in the Chloride Ion Channel Gene Clcn2 Associates with Atrial Fibrillation.Scientific reports · 2020Article
- Caveolae-Mediated Activation of Mechanosensitive Chloride Channels in Pulmonary Veins Triggers Atrial Arrhythmogenesis.Journal of the American Heart Association · 2019Article
- Research and progress on ClC‑2 (Review).Molecular medicine reports · 2017Review
- Heart-specific overexpression of the human short CLC-3 chloride channel isoform limits myocardial ischemia-induced ERP and QT prolongation.International journal of cardiology · 2016Article
- The impact of Cystic Fibrosis Transmembrane Regulator Disruption on cardiac function and stress response.Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society · 2016Article
- Effect of Different Formulations of Magnesium Chloride Used As Anesthetic Agents on the Performance of the Isolated Heart ofFrontiers in physiology · 2016Article
- The rs3737964 single-nucleotide polymorphism of the chloride channel-6 gene as a risk factor for coronary heart disease.Molecular genetics & genomic medicine · 2015Article
- Regulatory-auxiliary subunits of CLC chloride channel-transport proteins.The Journal of physiology · 2015Review
- Identification and characterization of the zebrafish ClC-2 chloride channel orthologs.Pflugers Archiv : European journal of physiology · 2015Article
- High glucose inhibits ClC-2 chloride channels and attenuates cell migration of rat keratinocytes.Drug design, development and therapy · 2015Article
- The importance of Ca(2+)-dependent mechanisms for the initiation of the heartbeat.Frontiers in physiology · 2015Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
A novel Cl(-) inward rectifier channel (Cl,ir) encoded by ClC-2, a member of the ClC voltage-gated Cl(-) channel gene superfamily, has been recently discovered in cardiac myocytes of several species. However, the physiological role of Cl,ir channels in the heart remains unknown. In this study we tested the hypothesis that Cl,ir channels may play an important role in cardiac pacemaker activity. In isolated guinea-pig sinoatrial node (SAN) cells, Cl,ir current was activated by hyperpolarization and hypotonic cell swelling. RT-PCR and immunohistological analyses confirmed the molecular expression of ClC-2 in guinea-pig SAN cells. Hypotonic stress increased the diastolic depolarization slope and decreased the maximum diastolic potential, action potential amplitude, APD(50), APD(90), and the cycle-length of the SAN cells. These effects were largely reversed by intracellular dialysis of anti-ClC-2 antibody, which significantly inhibited Cl,ir current but not other pacemaker currents, including the hyperpolarization-activated non-selective cationic "funny" current (I(f)), the L-type Ca(2+) currents (I(Ca,L)), the slowly-activating delayed rectifier I(Ks) and the volume-regulated outwardly-rectifying Cl(-) current (I(Cl,vol)). Telemetry electrocardiograph studies in conscious ClC-2 knockout (Clcn2(-/-)) mice revealed a decreased chronotropic response to acute exercise stress when compared to their age-matched Clcn2(+/+) and Clcn2(+/-) littermates. Targeted inactivation of ClC-2 does not alter intrinsic heart rate but prevented the positive chronotropic effect of acute exercise stress through a sympathetic regulation of ClC-2 channels. These results provide compelling evidence that ClC-2-encoded endogenous Cl,ir channels may play an important role in the regulation of cardiac pacemaker activity, which may become more prominent under stressed or pathological conditions.
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Registered trials
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 OpenQuestion graph.