ArticleJournal of cardiovascular pharmacology2006
Constitutively active Src tyrosine kinase changes gating of HCN4 channels through direct binding to the channel proteins.
Article in Journal of cardiovascular pharmacology, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 45 citations in OpenAlex.
- Glucocorticoids Selectively Inhibit Hippocampal CA1 Pyramidal Neurons Activity Through HCN Channels.International journal of molecular sciences · 2024Article
- Regulation of HCN Channels by Protein Interactions.Frontiers in physiology · 2022Review
- Review: HCN Channels in the Heart.Current cardiology reviews · 2022Review
- Cohesin-protein Shugoshin-1 controls cardiac automaticity via HCN4 pacemaker channel.Nature communications · 2021Article
- Comparing pathways for long-term heart rate modulation by the funny current.The Journal of general physiology · 2019Article
- HCN Channels: New Therapeutic Targets for Pain Treatment.Molecules (Basel, Switzerland) · 2018Review
- Crizotinib Inhibits Hyperpolarization-activated Cyclic Nucleotide-Gated Channel 4 Activity.Cardio-oncology (London, England) · 2017Article
- Stress Impairs Prefrontal Cortical Function via D1 Dopamine Receptor Interactions With Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels.Biological psychiatry · 2015Article
- EP2 Induces p38 Phosphorylation via the Activation of Src in HEK 293 Cells.Biomolecules & therapeutics · 2015Article
- Serotonergic regulation of excitability of principal cells of the dorsal cochlear nucleus.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2015Article
- HCN channels--modulators of cardiac and neuronal excitability.International journal of molecular sciences · 2015Review
- PP2 prevents β-adrenergic stimulation of cardiac pacemaker activity.Journal of cardiovascular pharmacology · 2014Article
- Exploring HCN channels as novel drug targets.Nature reviews. Drug discovery · 2011Review
- Downregulation of dendritic HCN channel gating in epilepsy is mediated by altered phosphorylation signaling.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2010Article
- Rescue of a trafficking defective human pacemaker channel via a novel mechanism: roles of Src, Fyn, and Yes tyrosine kinases.The Journal of biological chemistry · 2009Article
- Voltage-dependent opening of HCN channels: Facilitation or inhibition by the phytoestrogen, genistein, is determined by the activation status of the cyclic nucleotide gating ring.Biochimica et biophysica acta · 2009Article
- Associated changes in HCN2 and HCN4 transcripts and I(f) pacemaker current in myocytes.Biochimica et biophysica acta · 2009Article
- Activation of (Na+ + K+)-ATPase modulates cardiac L-type Ca2+ channel function.Molecular pharmacology · 2009Article
- Age-dependent differences in the inhibition of HCN2 current in rat ventricular myocytes by the tyrosine kinase inhibitor erbstatin.Pflugers Archiv : European journal of physiology · 2009Article
- Novel mechanism for suppression of hyperpolarization-activated cyclic nucleotide-gated pacemaker channels by receptor-like tyrosine phosphatase-alpha.The Journal of biological chemistry · 2008Article
Corrections and comments
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Authors and funding
3 authors at 3 institutions in 1 country.
Funding
Abstract
Cardiac pacemaker current, if, is generated by hyperpolarization-activated cyclic nucleotide-gated (HCN) channels. Our previous studies demonstrated that altered tyrosine phosphorylation can modulate the properties of both if and HCN channels. To assess a hypothesis that the intracellular tyrosine kinase Src may play a role in modulation by tyrosine phosphorylation of if, we cotransfected HEK293 cells with HCN4 and Src proteins. When HCN4 was cotransfected with a constitutively activated Src protein (Src529), the resultant voltage-dependent HCN4 activation was positively shifted (HCN4: V1/2 = -93 mV; Src529: V1/2 = -80 mV). The activation kinetics were accelerated at some potentials but not over the entire voltage range tested (eg, at -95 mV, tau_act(HCN4) = 3,243 ms; tau_act(Src529) = 1,113 ms). When HCN4 was cotransfected with a dominant negative Src protein (Src296), the HCN4 activation was shifted more negative to a smaller degree (HCN4: V1/2 = -93 mV; Src296: V1/2 = -98 mV; statistically insignificant) and the activation kinetics were slowed at most test potentials (eg, at -95 mV, tau_act(Src296) = 7,396 ms). Neither Src529 nor Src296 significantly altered HCN4 current density. Coimmunoprecipitation experiments revealed that Src forms a complex with HCN4 in HEK293 cells and in rat ventricular myocytes. Our data provide a novel mechanism of if regulation by Src tyrosine phosphorylation.
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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.