Regulation of the lateral wall stiffness by acetylcholine and GABA in the outer hair cells of the guinea pig

Abstract

Acetylcholine (ACh) and GABA, the main neurotransmitters of the efferent innervation of the outer hair cells (OHCs), are assumed to regulate the efficacy of the cochlear amplifier through a variety of mechanisms. The recently described stretch-induced changes of the lateral wall stiffness (regulatory stiffness response) and the stretch-induced slow cell motility of OHCs may be important regulatory mechanisms in this process. We found that ACh in cochleobasal OHCs significantly reduces the stiffness of the lateral wall but increases the regulatory stiffness response and stretch-induced slow cell motility. Qualitatively similar cellular responses were evoked by GABA in cochleoapical OHCs. The effects of ACh could be inhibited by strychnine, the specific inhibitor of the alpha(9) ACh receptors expressed in OHCs, whereas the effects of GABA could be blocked by bicuculline, a specific GABA(A) receptor antagonist. In the absence of extracellular Ca(2+) the effects of ACh and GABA on the regulatory stiffness response were reduced, indicating the involvement of Ca(2+) in the control of this process. Based on our results we suggest that efferent innervation protects the organ of Corti against high sound intensities and supports adaptation by modification of the micromechanical properties of OHCs. This could be governed by ACh and GABA indirectly, via the potentiation of stretch-induced cell shortening in a Ca(2+)-dependent manner, rather than by a direct stiffness regulation-related mechanism.