Apical phosphatidylserine externalization in auditory hair cells.
In hair cells of the inner ear, phosphatidylserine (PS), detected with fluorescent annexin V labeling, was rapidly exposed on the external leaflet of apical plasma membranes upon dissection of the organ of Corti. PS externalization was unchanged by caspase inhibition, suggesting that externalization did not portend apoptosis or necrosis. Consistent with that conclusion, mitochondrial membrane potential and hair-cell nuclear structure remained normal during externalization. PS externalization was triggered by forskolin, which raises cAMP, and blocked by inhibitors of adenylyl cyclase. Blocking Na(+) influx by inhibiting the mechanoelectrical transduction channels and P2X ATP channels also inhibited external PS externalization. Diminished PS externalization was also seen in cells exposed to LY 294002, which blocks membrane recycling in hair cells by inhibiting phosphatidylinositol 3-kinase. These results indicate that PS exposure on the external leaflet, presumably requiring vesicular transport, results from elevation of intracellular cAMP, which can be triggered by Na(+) entry into hair cells.
Shi
Xiaorui
X
Oregon Hearing Research Center (NRC04), Department of Otolaryngology, Head and Neck Surgery, Oregon Health & Science University, Portland, Oregon 97239, USA.
Gillespie
Peter G
PG
Nuttall
Alfred L
AL
D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000067956:Adenylyl Cyclase Inhibitors; D000818:Animals; D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D016764:Cell Polarity / Q000187:drug effects; D002867:Chromones / Q000494:pharmacology; D003053:Cochlear Duct / Q000187:drug effects; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D005089:Exocytosis / Q000187:drug effects; D005260:Female; D006168:Guinea Pigs; D006198:Hair Cells, Auditory / Q000166:cytology / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D009025:Morpholines / Q000494:pharmacology; D009336:Necrosis; D010718:Phosphatidylserines / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D012964:Sodium / Q000378:metabolism
D000067956:Adenylyl Cyclase Inhibitors; D017304:Annexin A5; D002867:Chromones; D009025:Morpholines; D010718:Phosphatidylserines; D000081082:Phosphoinositide-3 Kinase Inhibitors; C017759:9-(tetrahydro-2-furyl)-adenine; D005576:Colforsin; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D012964:Sodium; D000242:Cyclic AMP; D000225:Adenine; D002118:Calcium