We are using structural and molecular biology techniques to identify components of the outer hair cell electromechanical transduction complex. We have previously suggested that voltage dependent changes in transmembrane protein assemblies would form the basis of this electromechanical transduction. We have now demonstrated that unitary components of the force generation mechanism form domains that generate force vectors that can be reoriented in the plane of the membrane. Relative movements between domains could allow substantial changes of cell shape without disrupting the unit structure of the lattice, thus allowing the plasma membrane to accommodate simultaneously to both fast (AC) and slow (DC) shape changes. Using immunocytochemistry we showed that besides actin and spectrin, the 4.1 and anion exchanger (AE) proteins are associated with plasma membrane at the site of force generation. We are proposing that the plasma membrane may be connected to the cortical actin-spectrin lattice of the outer hair cell through protein "pillars" formed by anion exchanger and 4.1 proteins. This coupling may be essential to funnel forces generated in the plane of the plasma membrane into the longitudinal axis of the cell. We have cloned a cDNA encoding a novel isoform of the AE2 protein from the guinea pig organ of Corti. This cDNA is generated by alternative splicing, using internal donor and acceptor sites producing a shift in the open reading frame. The deduced polypeptide has a conserved NH2-cytoplasmic domain and a strikingly different COOH terminus with two, instead of the fourteen membrane spanning regions common in AE proteins. This finding constitutes the initial effort towards understanding the possible role that AEs play as intramembranous structural proteins in the outer hair cells and their potential involvement in the fast electromotive process.