Membrane composition modulates prestin-associated charge movement.
The lateral membrane of the cochlear outer hair cell (OHC) is the site of a membrane-based motor that powers OHC electromotility, enabling amplification and fine-tuning of auditory signals. The OHC membrane protein prestin plays a central role in this process. We have previously shown that membrane cholesterol modulates the peak voltage of prestin-associated nonlinear capacitance in vivo and in vitro. The present study explores the effects of membrane cholesterol and docosahexaenoic acid content on the peak and magnitude of prestin-associated charge movement in a human embryonic kidney (HEK 293) cell model. Increasing membrane cholesterol results in a hyperpolarizing shift in the peak voltage of the nonlinear capacitance (Vpkc) and a decrease in the total charge movement. Both measures depend linearly on membrane cholesterol concentration. Incubation of cholesterol-loaded cells in cholesterol-free media partially restores the Vpkc toward normal values but does not have a compensatory effect on the total charge movement. Decreasing membrane cholesterol results in a depolarizing shift in Vpkc that is restored toward normal values upon incubation in cholesterol-free media. However, cholesterol depletion does not alter the magnitude of charge movement. In contrast, increasing membrane docosahexaenoic acid results in a hyperpolarizing shift in Vpkc that is accompanied by an increase in total charge movement. Our results quantify the relation between membrane cholesterol concentration and prestin-associated charge movement and enhance our understanding of how membrane composition modulates prestin function.
Sfondouris
John
J
Bobby R. Alford Department of Otolaryngology-Head and Neck Surgery, Baylor College of Medicine, Houston, Texas 77030, USA.
Rajagopalan
Lavanya
L
Pereira
Fred A
FA
Brownell
William E
WE
D000818:Animals; D027321:Anion Transport Proteins / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D002462:Cell Membrane / Q000502:physiology; D002465:Cell Movement; D002784:Cholesterol / Q000378:metabolism; D003001:Cloning, Molecular; D003051:Cochlea / Q000502:physiology*; D004553:Electric Conductivity; D004594:Electrophysiology; D005849:Gerbillinae; D006801:Humans; D008563:Membrane Lipids / Q000378:metabolism; D018408:Patch-Clamp Techniques; D000076988:Sulfate Transporters
D027321:Anion Transport Proteins; D008563:Membrane Lipids; C498719:SLC26A5 protein, human; D000076988:Sulfate Transporters; D002784:Cholesterol