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.

Functional Role of GABAergic Innervation of the Cochlea: Phenotypic Analysis of Mice Lacking GABAAReceptor Subunits α1, α2, α5, α6, β2, β3, or δ

“…GABA application on guinea pig OHCs can reduce electromotility, hyperpolarize the cells, and alter their stiffness (Sziklai et al, 1996;Batta et al, 2004). When present, these effects are (1) blocked by picrotoxin and potentiated by benzodiazepines (Gitter and Zenner, 1992), consistent with GABA A receptors, including a ␥ subunit, and (2) restricted to apical OHCs, consistent with evidence that GABAergic terminals in guinea pigs are restricted to apical OHCs (Fex and Altschuler, 1986).…”

“…This efferent effect is dominated by effects of ACh released by efferent terminals acting on the ␣9/␣10 complex of nicotinic ACh receptors on OHCs (Vetter et al, 1999). Given published reports of GABAergic effects on length and stiffness of isolated OHCs (Plinkert et al, 1993;Batta et al, 2004) and given the reported colocalization of GABAergic and cholinergic markers in efferent terminals on OHCs (Maison et al, 2003a), we wondered whether loss of GABA A receptor subunits might affect the magnitude or time course of efferentmediated cochlear suppression.…”

“…Some in vitro studies report that GABA elicits OHC hyperpolarization and changes in motility (Gitter and Zenner, 1992;Batta et al, 2004), whereas others report no effects (Dulon et al, 1990;Evans et al, 1996). In frog lateral line, GABA suppresses spontaneous afferent discharge (Mroz and Sewell, 1989); however, in guinea pig, GABA has no effect on spontaneous activity (Arnold et al, 1998).…”

DPOAE Intensity Increase at Individual Dominant Frequency after Short-Term Auditory Exposure

“…OHCs are generally considered to provide the high sensitivity and fine-tuning in the mammalian organ of Corti. Efferent innervation of the OHCs is reported to modify the efficacy of the amplifier mechanism [20–23]. …”

“…In turn, this effect enhances cochlear amplification, auditory sensitivity, and otoacoustic emission magnitude due to the electromotile activity increase in OHCs [7–9, 23]. The decrease in the axial and lateral wall stiffness parameters is a consequence of increasing intracellular [Ca 2+ ] i levels in OHCs that is secondary to the sustained effect of efferent neurotransmitters [7, 26, 27].…”