Membrane disruption: An early event of hair cell apoptosis induced by exposure to intense noise

Membrane leakage has been found in hair cells undergoing apoptosis following exposure to intense noise. However, it is not known whether this membrane damage is the consequence of apoptotic degeneration or direct mechanical stress. The current study was designed to investigate whether membrane damage occurred before the onset of apoptosis and to determine the level of the membrane damage. Chinchillas were exposed to an impulse noise at 155 dB peak SPL. The noise-induced membrane damage was assessed functionally, using membrane tracers with graded molecular sizes (propidium iodide and FITC-dextrans with molecular sizes of 3, 40, 500, and 2000 kDa), and morphologically, using DiO staining and semithin sections. The study revealed two major findings. First, exposure to intense noise caused a rapid increase in membrane permeability, and the onset of membrane leakage preceded the manifestation of nuclear condensation. This indicates that the early membrane damage observed in apoptosis is the direct consequence of mechanical stress. Second, the level of membrane damage was severe, allowing the entry of 3 kDa and 40 kDa FITC-dextrans, but the membrane was not completely broken down, as evidenced by the preservation of the ability to exclude 500 kDa and 2000 kDa FITC-dextran molecules and the maintenance of the cell boundary. Notably, despite the membrane damage, hair cells continue to undergo the apoptotic process, leading to the generation of a type of apoptosis with early membrane damage.