(R2301) The Deafening Importance of Aquaporin-4: The Role of Potassium Regulation in Hearing Loss

Toluwalase Akintola (Mahtomedi High School)| Smriti Samtani (Mahtomedi High School)| Kaelyn Chen (Mahtomedi High School)| Katelyn Lawrence (Mahtomedi High School)| Evelyn Cegielski (Mahtomedi High School)| Anna Thompson (Mahtomedi High School)| Jim Lane (Mahtomedi High School)

Hearing is heavily dependent on Aquaporin 4 (AQP4), the principal protein that facilitates water transport through the cell membrane of epithelial supporting cells in the inner ear, which also house the potassium channels responsible for recycling and regulating K+ ions, thus playing a vital role in the equilibration of the cellular volume in response to transcellular K+ fluxes. When the AQP4 is unable to maintain equilibrium within the cell, it dramatically affects the potassium cycle and ultimately deafness due to a lack of potassium ions in the endolymph, and the action potential isn’t enough to pass on the vibration to the brain. According to Nicchia, et. al, a study done in 2010 found a heterozygous missense mutation in the gene which causes an Asp/Glu substitution at position 184 (D184E) which leads to a change in the D-loop of the protein. The mutated D-loop is more hydrophobic, reducing water gating and thus, reducing water permeability. This upset in water equilibrium along with the mutation slowing down and reducing the swelling kinetics leads to deafness. In that study, the mutation reduced the rate of cell swelling by 34.7 percent. Similarly, when there is an AQP4 deficiency, the existing AQP4 is not enough to properly equilibrate the cellular volume, which lowers the endolymphatic K+ concentration, causing the individual to be hearing impaired. In this study, we examined the effects the mutation had on hearing loss and how that differed from the effects of simply having a deficiency in AQP4 to further understand its role in hearing loss. The Mahtomedi MSOE Center for BioMolecular Modeling MAPS Team used 3-D modeling and printing technology to examine structure-function relationships of AQP4 in the ear. The visual model will be a valuable tool in developing our story.