Document Detail


TRPV4 enhances the cellular uptake of aminoglycoside antibiotics.
MedLine Citation:
PMID:  18682499     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The cochlea and kidney are susceptible to aminoglycoside-induced toxicity. The non-selective cation channel TRPV4 is expressed in kidney distal tubule cells, and hair cells and the stria vascularis in the inner ear. To determine whether TRPV4 is involved in aminoglycoside trafficking, we generated a murine proximal-tubule cell line (KPT2) and a distal-tubule cell line (KDT3). TRPV4 expression was confirmed in KDT3 cells but not in KPT2 cells. Removal of extracellular Ca(2+) significantly enhanced gentamicin-Texas-Red (GTTR) uptake by KDT3, indicative of permeation through non-selective cation channels. To determine whether TRPV4 is permeable to GTTR, stable cell lines were generated that express TRPV4 in KPT2 (KPT2-TRPV4). KPT2-TRPV4 cells took up more GTTR than control cell lines (KPT2-pBabe) in the absence of extracellular Ca(2+). TRPV4-dependent GTTR uptake was abolished by a point mutation within the crucial pore region of the channel, suggesting that GTTR permeates the TRPV4 channel. In an endolymph-like extracellular environment, clearance of GTTR was attenuated from KPT2-TRPV4 cells in a TRPV4-dependent fashion. We propose that TRPV4 has a role in aminoglycoside uptake and retention in the cochlea.
Authors:
Takatoshi Karasawa; Qi Wang; Yi Fu; David M Cohen; Peter S Steyger
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2008-08-05
Journal Detail:
Title:  Journal of cell science     Volume:  121     ISSN:  0021-9533     ISO Abbreviation:  J. Cell. Sci.     Publication Date:  2008 Sep 
Date Detail:
Created Date:  2008-08-21     Completed Date:  2008-10-30     Revised Date:  2014-09-13    
Medline Journal Info:
Nlm Unique ID:  0052457     Medline TA:  J Cell Sci     Country:  England    
Other Details:
Languages:  eng     Pagination:  2871-9     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Aminoglycosides / metabolism*
Animals
Anti-Bacterial Agents / metabolism*
Calcium / pharmacology
Cell Line
Dogs
Ear, Inner / cytology,  metabolism
Endolymph / drug effects,  metabolism
Extracellular Space / drug effects,  metabolism
Gentamicins / metabolism
Kidney / cytology,  metabolism
Methionine / metabolism
Mice
Rats
TRPV Cation Channels / metabolism*
Xanthenes / metabolism
Grant Support
ID/Acronym/Agency:
DC04555/DC/NIDCD NIH HHS; F32 DC008465/DC/NIDCD NIH HHS; F32 DC008465/DC/NIDCD NIH HHS; F32 DC008465-01A1/DC/NIDCD NIH HHS; F32 DC008465-02/DC/NIDCD NIH HHS; P30 DC005983/DC/NIDCD NIH HHS; P30 DC005983-03/DC/NIDCD NIH HHS; P30 DC005983-04/DC/NIDCD NIH HHS; P30 DC005983-05/DC/NIDCD NIH HHS; P30 DC05983/DC/NIDCD NIH HHS; R01 DC004555/DC/NIDCD NIH HHS; R01 DC004555-04/DC/NIDCD NIH HHS; R01 DC004555-05/DC/NIDCD NIH HHS; T32 DC005945/DC/NIDCD NIH HHS
Chemical
Reg. No./Substance:
0/Aminoglycosides; 0/Anti-Bacterial Agents; 0/Gentamicins; 0/TRPV Cation Channels; 0/Trpv4 protein, rat; 0/Xanthenes; 82354-19-6/Texas red; AE28F7PNPL/Methionine; SY7Q814VUP/Calcium
Comments/Corrections

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