Microdomains Shift and Rotate in the Lateral Wall of Cochlear Outer hair cells

Outer hair cell (OHC) electromotility, a response consisting of reversible changes in cell length and diameter induced by electrical stimulation, confers remarkable sensitivity and frequency resolution to the mammalian inner ear. Looking for a better understanding of this mechanism, we labeled isolated guinea pig OHCs with microspheres and, using high-speed video recording, investigated their movements at the apical, mid, and basal regions of osmotically and electrically stimulated cells. After hypoosmotic challenge, OHCs shortened and their diameter increased, with microspheres moving always toward the central plane; iso-osmolarity returned OHCs to their original shape and microspheres to their original positions. Under electrical stimulation, microspheres exhibited robust movements, with their displacement vectors changing in direction from random to parallel to the longitudinal axis of the cells with peak reorientation speeds of up to 6 rad/s and returning to random after 5 min without stimulation. Alterations in plasma-membrane cholesterol levels as well as cytoskeleton integrity affected microsphere responses. We concluded that microspheres attach to different molecular microdomains, and these microdomains are able to shift and rotate in the plane of the OHC lateral wall with a dynamics tightly regulated by membrane lipid composition and the cortical cytoskeleton.