ArticleThe Journal of general physiology2022
The funny current If is essential for the fight-or-flight response in cardiac pacemaker cells.
Article in The Journal of general physiology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 6 citations in OpenAlex.
- The Binding of Fibroblast Growth Factor 23 (FGF23) to FGF Receptor-αKlotho Complex Increases Sinoatrial Electrical Activity.Acta physiologica (Oxford, England) · 2026Article
- L-Type CaCirculation research · 2026Article
- Pacemaker Channels and the Chronotropic Response in Health and Disease.Circulation research · 2024Review
- Identifying sex similarities and differences in structure and function of the sinoatrial node in the mouse heart.Frontiers in medicine · 2024Article
- Ventromedial hypothalamus relays chronic stress inputs and exerts bidirectional regulation on anxiety state and related sympathetic activity.Frontiers in cellular neuroscience · 2023Article
- INNOVATIVE TECHNIQUES AND NEW INSIGHTS: Studying cardiac ionic currents and action potentials in physiologically relevant conditions.Physiological mini-reviewsArticle
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
The sympathetic nervous system fight-or-flight response is characterized by a rapid increase in heart rate, which is mediated by an increase in the spontaneous action potential (AP) firing rate of pacemaker cells in the sinoatrial node. Sympathetic neurons stimulate sinoatrial myocytes (SAMs) by activating β adrenergic receptors (βARs) and increasing cAMP. The funny current (If) is among the cAMP-sensitive currents in SAMs. If is critical for pacemaker activity, however, its role in the fight-or-flight response remains controversial. In this study, we used AP waveform analysis, machine learning, and dynamic clamp experiments in acutely isolated SAMs from mice to quantitatively define the AP waveform changes and role of If in the fight-or-flight increase in AP firing rate. We found that while βAR stimulation significantly altered nearly all AP waveform parameters, the increase in firing rate was only correlated with changes in a subset of parameters (diastolic duration, late AP duration, and diastolic depolarization rate). Dynamic clamp injection of the βAR-sensitive component of If showed that it accounts for ∼41% of the fight-or-flight increase in AP firing rate and 60% of the decrease in the interval between APs. Thus, If is an essential contributor to the fight-or-flight increase in heart rate.
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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.