Hemichannel-mediated inositol 1,4,5-trisphosphate (IP3) release in the cochlea: a novel mechanism of IP3 intercellular signaling.

David G. Gossman, Hong Bo Zhao

Research output: Contribution to journalArticlepeer-review

52 Scopus citations

Abstract

Inositol 1,4,5-trisphosphate (IP(3)) is an important second messenger that can trigger a Ca(2+) wave prolongated between cells. This intercellular signaling was found defective in some gap junction connexin deafness mutants. In this study, the mechanism underlying IP(3) intercellular signaling in the cochlea was investigated. A gap junction channel is composed of two hemichannels. By using a fluorescence polarization technique to measure IP(3) concentration, the authors found that IP(3) could be released by gap junction hemichannels in the cochlea. The IP(3) release was increased about three- to fivefold by the reduction of extracellular Ca(2+) concentration or by mechanical stress. This incremental release could be blocked by gap junction blockers but not eliminated by a purinergic P2x receptor antagonist and verapamil, which is a selective P-glycoprotein inhibitor inhibiting the ATP-binding cassette transporters. The authors also found that IP(3) receptors were extensively expressed in the cochlear sensory epithelium, including on the cell surface. Extracellular application of IP(3) could trigger cellular Ca(2+) elevation. This Ca(2+) elevation was eliminated by the gap junction hemichannel blocker. These data reveal that IP(3) can pass through hemichannels acting as an extracellular mediator to participate in intercellular signaling. This hemichannel-mediated extracellular pathway may play an important role in long-distance intercellular communication in the cochlea, given that IP(3) only has a short lifetime in the cytoplasm.

Original languageEnglish
Pages (from-to)305-315
Number of pages11
JournalCell communication & adhesion
Volume15
Issue number4
DOIs
StatePublished - Nov 2008

Bibliographical note

Funding Information:
This work was supported by a grant (R01 DC 05989) from the National Institute of Deafness and Other Communication Disorders. Address correspondence to Hong-Bo Zhao, PhD, MD, Associate Professor, Department of Surgery*Otolaryngology, University of Kentucky Medical Center, 800 Rose Street, Lexington, KY 40536-0293, USA. E-mail: hzhao2@uky.edu

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology

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