ArticleProceedings of the National Academy of Sciences of the United States of America2008
ATP release through connexin hemichannels and gap junction transfer of second messengers propagate Ca2+ signals across the inner ear.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 219 papers.
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Who cites it
219 citing papers in PubMed, 340 citations in OpenAlex.
- Spontaneous Calcium Signalling in the Developing Mammalian Cochlea.Journal of the Association for Research in Otolaryngology : JARO · 2026Review
- Recent Progress in Mechanism-Based Therapies forInternational journal of molecular sciences · 2026Review
- Small Cell Lung Cancer Establishes a Metabolic Autocrine Mechanism Through Active Extracellular ATP Transport.Cancer science · 2026Article
- Exploring Embryonic and Postnatal Gene Therapy Approaches for GJB2-Related Deafness: A Scoping Review.Audiology research · 2026Review
- Spontaneous CaExperimental physiology · 2026Article
- ATP release mediated by TRPM3 enhances invasion in glioblastoma.Animal cells and systems · 2026Article
- Article
- Connexin hemichannel blockade by abEC1.1 disrupts glioblastoma progression, suppresses invasiveness, and reduces hyperexcitability in preclinical models.Cell communication and signaling : CCS · 2025Article
- Distinct Connexin43, Connexin31, and Pannexin1 expression patterns in the cochlea of a non-human primate.Scientific reports · 2025Article
- Kolliker's Organ and Its Functional Role in the Development of Corti's Organ and Auditory Systems.Audiology research · 2025Review
- Molecular Interplay Between Non-Coding RNAs and Connexins and Its Possible Role in Cancer.International journal of molecular sciences · 2025Review
- Deletion of murine astrocytic vesicular nucleotide transporter increases anxiety and depressive-like behavior and attenuates motivation for reward.Molecular psychiatry · 2025Article
- A rare haplotype of the GJD3 gene segregating in familial Meniere's disease interferes with connexin assembly.Genome medicine · 2025Article
- Tracheal tuft cells release ATP and link innate to adaptive immunity in pneumonia.Nature communications · 2025Article
- Boldine as a neuroprotective agent against motor neuron degeneration in models of amyotrophic lateral sclerosis.Frontiers in cellular neuroscience · 2025Article
- Connexins 43 and 45 hemichannels mediate ATP release in the urinary bladder.Bladder (San Francisco, Calif.) · 2025Article
- Mechanisms driving the functional maturation of the developing mammalian auditory pathway.Current topics in developmental biology · 2025Review
- A fully human IgG1 antibody targeting connexin 32 extracellular domain blocks CMTX1 hemichannel dysfunction in an in vitro model.Cell communication and signaling : CCS · 2024Article
- Common genetic etiologies of sensorineural hearing loss in Koreans.Genomics & informatics · 2024Review
- An Ala/Glu difference in E1 of Cx26 and Cx30 contributes to their differential anionic permeabilities.The Journal of general physiology · 2024Article
159 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 6 institutions in 4 countries.
Funding
Abstract
Extracellular ATP controls various signaling systems including propagation of intercellular Ca(2+) signals (ICS). Connexin hemichannels, P2x7 receptors (P2x7Rs), pannexin channels, anion channels, vesicles, and transporters are putative conduits for ATP release, but their involvement in ICS remains controversial. We investigated ICS in cochlear organotypic cultures, in which ATP acts as an IP(3)-generating agonist and evokes Ca(2+) responses that have been linked to noise-induced hearing loss and development of hair cell-afferent synapses. Focal delivery of ATP or photostimulation with caged IP(3) elicited Ca(2+) responses that spread radially to several orders of unstimulated cells. Furthermore, we recorded robust Ca(2+) signals from an ATP biosensor apposed to supporting cells outside the photostimulated area in WT cultures. ICS propagated normally in cultures lacking either P2x7R or pannexin-1 (Px1), as well as in WT cultures exposed to blockers of anion channels. By contrast, Ca(2+) responses failed to propagate in cultures with defective expression of connexin 26 (Cx26) or Cx30. A companion paper demonstrates that, if expression of either Cx26 or Cx30 is blocked, expression of the other is markedly down-regulated in the outer sulcus. Lanthanum, a connexin hemichannel blocker that does not affect gap junction (GJ) channels when applied extracellularly, limited the propagation of Ca(2+) responses to cells adjacent to the photostimulated area. Our results demonstrate that these connexins play a dual crucial role in inner ear Ca(2+) signaling: as hemichannels, they promote ATP release, sustaining long-range ICS propagation; as GJ channels, they allow diffusion of Ca(2+)-mobilizing second messengers across coupled cells.
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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.