Apical phosphatidylserine externalization in auditory hair cells

Area of Science:

• Inner ear biology
• Cellular physiology
• Membrane trafficking

Background:

• Phosphatidylserine (PS) exposure on the cell surface typically signals apoptosis or necrosis.
• Inner ear hair cells play a critical role in hearing and balance.

Purpose of the Study:

• To investigate the mechanism and significance of phosphatidylserine (PS) externalization in inner ear hair cells.
• To determine if PS externalization in hair cells indicates cell death.

Main Methods:

• Utilized fluorescent annexin V labeling to detect PS exposure on hair cell membranes.
• Employed forskolin to induce cAMP elevation and adenylyl cyclase inhibitors to block it.
• Investigated the role of Na(+) influx by inhibiting mechanoelectrical transduction and P2X ATP channels.
• Assessed the impact of phosphatidylinositol 3-kinase (PI3K) inhibition on PS externalization and membrane recycling.

Main Results:

• Rapid PS externalization occurred on apical plasma membranes of hair cells upon dissection.
• PS externalization was not affected by caspase inhibition and was independent of apoptosis or necrosis markers (mitochondrial membrane potential, nuclear structure).
• Forskolin-induced elevation of intracellular cAMP triggered PS externalization, while adenylyl cyclase inhibitors blocked it.
• Inhibition of Na(+) influx and PI3K (blocking membrane recycling) also reduced PS externalization.

Conclusions:

• PS externalization in inner ear hair cells does not indicate cell death.
• Elevated intracellular cAMP, triggered by Na(+) influx, is a primary driver of PS externalization.
• Membrane recycling processes, regulated by PI3K, also influence PS exposure on hair cell membranes.