title: Chloride-driven electromechanical phase lags at acoustic frequencies are generated by SLC26a5, the outer hair cell motor protein.
abstract: Outer hair cells (OHC) possess voltage-dependent membrane bound molecular motors, identified as the solute carrier protein SLC26a5, that drive somatic motility at acoustic frequencies. The electromotility (eM) of OHCs provides for cochlear amplification, a process that enhances auditory sensitivity by up to three orders of magnitude. In this study, using whole cell voltage clamp and mechanical measurement techniques, we identify disparities between voltage sensing and eM that result from stretched exponential electromechanical behavior of SLC26a5, also known as prestin, for its fast responsiveness. This stretched exponential behavior, which we accurately recapitulate with a new kinetic model, the meno presto model of prestin, influences the protein's responsiveness to chloride binding and provides for delays in eM relative to membrane voltage driving force. The model predicts that in the frequency domain, these delays would result in eM phase lags that we confirm by measuring OHC eM at acoustic frequencies. These lags may contribute to canceling viscous drag, a requirement for many models of cochlear amplification.
authors.affiliation: Surgery (Otolaryngology), Yale University School of Medicine, New Haven, Connecticut; Neurobiology, Yale University School of Medicine, New Haven, Connecticut; Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, Connecticut. Electronic address: joseph.santos-sacchi@yale.edu.
authors.forename: Joseph
authors.initials: J
authors.lastname: Santos-Sacchi
authors.affiliation: Surgery (Otolaryngology), Yale University School of Medicine, New Haven, Connecticut.
authors.forename: Lei
authors.initials: L
authors.lastname: Song
mesh_terms: D000818:Animals; D002465:Cell Movement; D002712:Chlorides / Q000378:metabolism; D006168:Guinea Pigs; D018072:Hair Cells, Auditory, Outer / Q000378:metabolism* / Q000502:physiology; D008564:Membrane Potentials; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry / Q000378:metabolism*; D011930:Reaction Time; D013016:Sound
chemical_list: D002712:Chlorides; C498722:Pres protein, Cavia porcellus; D011506:Proteins