Spectrin, actin and the structure of the cortical lattice in mammalian cochlear outer hair cells

Abstract

Mammalian cochlear outer hair cells generate high-frequency forces in response to electrical stimulation. Force generation occurs in the lateral cortex of the cell, which includes the plasma membrane, a two-dimensional ‘cortical lattice’ of filamentous protein, and a multi-layered membrane system, the lateral cisternae. The cortical lattice is composed of relatively long filaments, 6.7 nm in diameter, which are wound circumferentially about the cell. These filaments are spaced about 42 nm apart and are cross-linked by a second type of filament 3.2 nm in diameter approximately aligned with the longitudinal axis of the cell. The cortical lattice is the only cortical structure that remains after the cell is fully extracted in the detergent Triton X-100 and high-salt solution. It retains the original cylindrical shape of the cell and is reversibly deformable. Antibodies raised against chicken gizzard actin, human blood spectrin and pig brain spectrin all react positively with the extracted lattice viewed using immunofluorescence. Three protein subunits identified in the organ of Corti have approximate molecular weights of 220, 235 and 240K (K = 10(3) Mr) and react with the spectrin antibodies. A structural model of the lattice is proposed in which the circumferential filaments are composed of actin and the cross-linked of spectrin. The model can account for the unusual cylindrical shape of outer hair cells and suggests a mechanism of force generation based upon the elastic and electrostatic properties of spectrin.