Difference in Metabolic Rates Could be Responsible for Increased Cell Death Among Outer Hair Cells as Compared to Inner Hair Cells in Response to Trauma

OMAHA—Richard Hallworth, Ph.D., of Creighton University School of Medicine, Omaha, Nebraska, and colleagues describe differences in response to aminoglycoside among inner and outer cochlear hair cells in the March 6 issue of the journal Brian Research. Dr. Hallworth’s research was sponsored in part by the American Hearing Research Foundation.

Hair cells are found in the organ of Corti in the cochlea of the inner ear, and are the sensory cells that translate sound vibrations into nerve impulses that give rise to hearing. The loss of hair cells is a major cause of hearing loss. One of the major ways hair cells get damaged or killed is by loud noise – either over time (as for someone who works in a noisy environment) or a single incident of exposure to loud noises (such as a soldier under gun or mortar fire). Hair cells can also be damaged by antibiotics of the aminoglycoside class, which are used to treat gram-negative infections such as septicemia and some urinary tract infections. Gentamicin is a commonly-used aminoglycoside.

Dr. Hallworth and colleagues investigated the biochemical process associated with metabolism within hair cells that lead to their death.

“There is an association between the extra metabolic demand by hair cells under stress by noise or aminoglycoside and hair cell death,” says Hallworth.

The research team dissected out cochleae from mice, and kept them alive and functional in the lab for several hours. During this time, they applied aminoglycoside and using live cell imaging, were able to determine the metabolic rates of both the inner and outer hair cells by noting levels of NADH (nicotinamide adenine dinucleotide). NADH is a metabolic intermediate product produced in the mitochondria. Low levels of NADH indicate increased metabolism.

The sensory part of the cochlea, where conversion of sound energy to neural excitation takes place, is called the organ of Corti. It consists of a sheet of two types of hair cells called inner hair cells (IHCs) and outer hair cells (OHCs). OHCs have been found to be more vulnerable to damage by noise and aminoglycosides than IHCs.

The researchers found that, after applying gentamicin to the cochlea, the NADH levels fell over time in the OHCs but not the IHCs. This suggests that gentamicin is causing an increase in metabolism in the OHCs. Revving up the metabolism could certainly be the first step in causing the OHCs to die, explains Dr. Hallworth.

Hair cells, like many other cell types are vulnerable to damage by reactive oxygen species, or so called “free radicals”, which are produced during metabolism. High levels of free radicals in a cell can trigger the cell’s own “suicide” system, called apoptosis, causing it to die.

Dr. Hallworth concludes that increased metabolism in the OHCs in response to stress (caused in this case by aminoglycoside) could be responsible for the extra cell death seen among OHCs.