» Articles » PMID: 32384538

A Novel Theoretical Framework Reveals More Than One Voltage-sensing Pathway in the Lateral Membrane of Outer Hair Cells

Overview
Journal J Gen Physiol
Specialty Physiology
Date 2020 May 9
PMID 32384538
Citations 1
Authors
Affiliations
Soon will be listed here.
Abstract

Outer hair cell (OHC) electromotility amplifies acoustic vibrations throughout the frequency range of hearing. Electromotility requires that the lateral membrane protein prestin undergo a conformational change upon changes in the membrane potential to produce an associated displacement charge. The magnitude of the charge displaced and the mid-reaction potential (when one half of the charge is displaced) reflects whether the cells will produce sufficient gain at the resting membrane potential to boost sound in vivo. Voltage clamp measurements performed under near-identical conditions ex vivo show the charge density and mid-reaction potential are not always the same, confounding interpretation of the results. We compare the displacement charge measurements in OHCs from rodents with a theory shown to exhibit good agreement with in silico simulations of voltage-sensing reactions in membranes. This model equates the charge density to the potential difference between two pseudo-equilibrium states of the sensors when they are in a stable conformation and not contributing to the displacement current. The model predicts this potential difference to be one half of its value midway into the reaction, when one equilibrium conformation transforms to the other pseudo-state. In agreement with the model, we find the measured mid-reaction potential to increase as the charge density decreases to exhibit a negative slope of ∼1/2. This relationship suggests that the prestin sensors exhibit more than one stable hyperpolarized state and that voltage sensing occurs by more than one pathway. We determine the electric parameters for prestin sensors and use the analytical expressions of the theory to estimate the energy barriers for the two voltage-dependent pathways. This analysis explains the experimental results, supports the theoretical approach, and suggests that voltage sensing occurs by more than one pathway to enable amplification throughout the frequency range of hearing.

Citing Articles

The cochlear outer hair cell speed paradox.

Rabbitt R Proc Natl Acad Sci U S A. 2020; 117(36):21880-21888.

PMID: 32848062 PMC: 7486750. DOI: 10.1073/pnas.2003838117.

References
1.
Rajagopalan L, Organ-Darling L, Liu H, Davidson A, Raphael R, Brownell W . Glycosylation regulates prestin cellular activity. J Assoc Res Otolaryngol. 2009; 11(1):39-51. PMC: 2820205. DOI: 10.1007/s10162-009-0196-5. View

2.
Joshi H, Watson D, LABHSETWAR A . Ovarian secretion of oestradiol, oestrone, 20-dihydroprogesterone and progesterone during the oestrous cycle of the guinea-pig. J Reprod Fertil. 1973; 35(1):177-81. DOI: 10.1530/jrf.0.0350177. View

3.
Lomize M, Pogozheva I, Joo H, Mosberg H, Lomize A . OPM database and PPM web server: resources for positioning of proteins in membranes. Nucleic Acids Res. 2011; 40(Database issue):D370-6. PMC: 3245162. DOI: 10.1093/nar/gkr703. View

4.
Keiler S, Richter C . Cochlear dimensions obtained in hemicochleae of four different strains of mice: CBA/CaJ, 129/CD1, 129/SvEv and C57BL/6J. Hear Res. 2001; 162(1-2):91-104. DOI: 10.1016/s0378-5955(01)00374-4. View

5.
FRANK G, Hemmert W, Gummer A . Limiting dynamics of high-frequency electromechanical transduction of outer hair cells. Proc Natl Acad Sci U S A. 1999; 96(8):4420-5. PMC: 16347. DOI: 10.1073/pnas.96.8.4420. View