Gap junctional hemichannel-mediated ATP release and hearing controls in the inner ear

Zhao, Hong-Bo; Yu, Ning; Fleming, Carrie R.

doi:10.1073/pnas.0506481102

Cited by 184 publications

(235 citation statements)

References 33 publications

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“…This study undertook to localize the expression of P2Y 1 , P2Y 2 , P2Y 4 , P2Y 6 , and P2Y 12 receptors in the developing rat cochlea utilizing specific antisera for these subtypes. With the exception of P2Y 12 , expression of all these receptors has previously been confirmed in rat cochlear tissues by RT-PCR [3,26].…”

Section: Rt-pcr Detection Of P2y12 Receptor Mrna Transcriptmentioning

confidence: 99%

“…The antiserum has previously been shown by Western Blot to specifically recognize the rat P2Y 1 epitope (63-kDa band) and the recombinant hP2Y1 protein [28]. P2Y 2 , P2Y 4 , P2Y 6 , and P2Y 12 antisera were obtained from Alomone Labs (Israel), who provided Western Blot data of their specificity. In addition, the P2Y 4 antiserum has been used to immunolocalise P2Y 4 expression in the cochlear lateral wall tissue of the adult Sprague-Dawley rat and gerbil [29].…”

Section: Rt-pcr Detection Of P2y12 Receptor Mrna Transcriptmentioning

confidence: 99%

“…ATP release has also been observed in the supporting cells in and adjacent to the organ of Corti [3][4][5] where the mechanism involves P2Y and P2X receptor signaling that could be induced by hair cell damage. Connexin and pannexin hemichannels are implicated in the ATP release mechanism [6][7][8]. The stria vascularis in the lateral wall of the cochlea is the source of the K + flux into scala media that establishes the driving force for sound transduction (the positive endocochlear potential).…”

Section: Introductionmentioning

confidence: 99%

“…This process also terminates P2X receptor activation and promotes selective activation of P2Y receptors, which have broader sensitivity to purines and pyrimidines (ATP, ADP, AMP, UTP, UDP, and di-adenosine polyphosphates). Eight mammalian P2Y receptors have been identified, and in the case of P2Y 1 , P2Y 2 , P2Y 4 , P2Y 6 , and P2Y 11 , they directly mediate Ca 2+ signaling via the G qa -phospholipase C b (PLC)-inositol trisphosphate (IP 3 )-gated Ca 2+ store pathway. P2Y 12 , P2Y 13 , and P2Y 14 receptor signal transduction utilizes G ia -mediated inhibition of adenylate cyclase and hence reduction in cAMP (reviewed by [14,15]).…”

Section: Introductionmentioning

confidence: 99%

“…The P2Y-PLC pathway may also mediate Ca 2+ entry through transient receptor potential (TRP) channels, gated by membranebound diacylglycerol (DAG) [16,17]. In broad terms, P2Y 1 and P2Y 11 are ATP preferring [14]; P2Y 12 and P2Y 13 are ADP preferring [14]; rat P2Y 2 and P2Y 4 orthologs are equally activated by ATP and UTP [18] and P2Y 6 is preferentially activated by UDP, with ADP > ATP [19]; P2Y 14 is activated most potently by UDP-glucose [14]. However, the functional significance of the agonist preferences of the P2Y receptors needs to be matched to the endogenous ligand environment.…”

Section: Introductionmentioning

confidence: 99%

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Differential expression of P2Y receptors in the rat cochlea during development

Huang

Thorne

Vlajkovic

et al. 2010

Purinergic Signalling

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Purinergic signaling has broad physiological significance to the hearing organ, involving signal transduction via ionotropic P2X receptors and metabotropic G-protein-coupled P2Y and P1 (adenosine), alongside conversion of nucleotides and nucleosides by ectonucleotidases and ecto-nucleoside diphosphokinase. In addition, ATP release is modulated by acoustic overstimulation or stress and involves feedback regulation. Many of these principal elements of the purinergic signaling complex have been well characterized in the cochlea, while the characterization of P2Y receptor expression is emerging. The present study used immunohistochemistry to evaluate the expression of five P2Y receptors, P2Y 1 , P2Y 2 , P2Y 4 , P2Y 6 , and P2Y 12 , during development of the rat cochlea. Commencing in the late embryonic period, the P2Y receptors studied were found in the cells lining the cochlear partition, associated with establishment of the electrochemical environment which provides the driving force for sound transduction. In addition, early postnatal P2Y 2 and P2Y 4 protein expression in the greater epithelial ridge, part of the developing hearing organ, supports the view that initiation and regulation of spontaneous activity in the hair cells prior to hearing onset is mediated by purinergic signaling. Sub-cellular compartmentalization of P2Y receptor expression in sensory hair cells, and diversity of receptor expression in the spiral ganglion neurons and their satellite cells, indicates roles for P2Y receptormediated Ca 2+ -signaling in sound transduction and auditory neuron excitability. Overall, the dynamics of P2Y receptor expression during development of the cochlea complement the other elements of the purinergic signaling complex and reinforce the significance of extracellular nucleotide and nucleoside signaling to hearing.

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Section: Rt-pcr Detection Of P2y12 Receptor Mrna Transcriptmentioning

confidence: 99%

Section: Rt-pcr Detection Of P2y12 Receptor Mrna Transcriptmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Differential expression of P2Y receptors in the rat cochlea during development

Huang

Thorne

Vlajkovic

et al. 2010

Purinergic Signalling

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Gap Junctions and Connexins: The Molecular Genetics of Deafness

Nickel

Forge

2010

Encyclopedia of Life Sciences

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Mutations in the gene GJB2 encoding the gap‐junction protein connexin 26 ( Cx26 ), in particular, and in GJB6 coding for connexin 30 ( Cx30 ) are the most common cause of autosomal recessive sensorineural hearing loss in many world populations. Variants of GJB2 are also associated with dominant forms of both nonsyndromic and syndromic deafness. A complex picture of the roles of gap junctions in cochlear physiology has emerged. Rather than being mere conduits for the circulation of potassium ions in the inner ear, gap junctions have been implicated in the maintenance of metabolic homeostasis and in intercellular signalling among nonsensory cells. Studies of mutant channels and mouse models for connexin ‐related deafness have provided valuable insights into the heterogeneous mechanisms by which connexin mutations may cause cochlear dysfunction. Despite recent advances it is still not fully understood what roles gap junctions play in the inner ear and how connexin mutations cause deafness. Key Concepts: GJB2 and GJB6 have been mapped to the DFNB1 locus, which accounts for up to 50% of all cases of autosomal recessive nonsyndromic hearing loss. Molecular genetic tests for DFNB1 should include DNA sequencing of the GJB2 exons and mutation analysis for GJB6 deletions. The identification of factors underlying the phenotypic variability of connexin‐related hearing loss may improve clinical diagnosis and genetic counselling. A better understanding of the role of gap‐junctional communication in the inner ear and the structure–function relationships of connexin proteins is required for the development of mechanism‐based treatments of connexin‐associated hearing loss.

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TWO INNEXINS OF Spodoptera litura INFLUENCES HEMICHANNEL AND GAP JUNCTION FUNCTIONS IN CELLULAR IMMUNE RESPONSES

Pang

et al. 2015

Arch Insect Biochem Physiol

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Insect cellular immune responses include encapsulation, nodule formation, and phagocytosis. Hemichannels and gap junctions are involved in these cellular actions. Innexins (Inxs: analogous to the vertebrate connexins) form hemichannels and gap junctions, but the molecular mechanisms underlying their biology is still unclear. In this article, we reported a steady-state level of Inxs (SpliInxs) in hemocytes of Spodoptera litura, which formed nonfunctional hemichannels on the cell surface to maintain normal metabolism. We also reported that two innnexins (SpliInx2 and SpliInx3) were expressed significantly higher in hemocytes compared to other tissues, suggesting that they play important roles in hemocytes. Amino acid analysis found that two cysteine residues in two extracellular loops provided the capability for SpliInx2 and SpliInx3 hemichannels to dock into gap junctions. Western blotting demonstrated that both extracellular and intracellular loops of SpliInx3 and the extracellular loops of SpliInx2 might undergo posttranslational modification during the formation of a steady-state hemichannel. During hemichannel formation, SpliInx2 presented as one isoform, while SpliInx3 presented as three isoforms. These results provide fundamental knowledge for further study of how steady-state levels of SpliInxs are dynamically adjusted to perform cellular immune responses under immune challenge.

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Gap junctional hemichannel-mediated ATP release and hearing controls in the inner ear

Cited by 184 publications

References 33 publications

Differential expression of P2Y receptors in the rat cochlea during development

Differential expression of P2Y receptors in the rat cochlea during development

Gap Junctions and Connexins: The Molecular Genetics of Deafness

TWO INNEXINS OF Spodoptera litura INFLUENCES HEMICHANNEL AND GAP JUNCTION FUNCTIONS IN CELLULAR IMMUNE RESPONSES

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