Effect of acetylcholine and GABA on the transfer function of electromotility in isolated outer hair cells

Outer hair cells (OHC) from high- and low-frequency regions were separately isolated from guinea pig cochleas. The cells were inserted with their ciliary pole first into a partitioning microchamber so that only 20-50% of the cell length was excluded. Somatic length changes due to transcellular electrical stimulation were measured at the cuticular plate in the inserted portion of the cells. Transfer curves of electromotility of the OHCs were obtained by both a series of brief (2.5 ms) and longer (30 ms) square pulses with opposite polarity and linearly increasing size from 40 to 280 mV in both negative and positive directions. Alterations in the transient and steady-state electromotility transfer curves were examined by application of acetylcholine (ACh) and gamma-aminobutyric acid (GABA) to the synaptic pole. ACh, in the concentration range of 10-30 microM, evoked a significant magnitude and gain increase of electromotility in both transient and steady-state responses without a measurable shift in the operating point of the displacement-voltage transfer curve. A tonotopic response magnitude difference is found for ACh challenge. Basal turn OHCs responded with greater magnitude increase (+90% increase from control) than apical turn OHCs (+40%). GABA exerted an opposite effect, again in a location-dependent manner. Magnitude response decreased about 30% for long cells and 14% for short ones. Atropin, a muscarinic receptor antagonist, completely blocked the increase in electromotility response due to ACh. However, D-tubocurarine, a nicorinic receptor antagonist, while not blocking the ACh effect, altered the cell's apparent operating point. Bicuculline methiodide, a GABAA-receptor antagonist, completely arrested GABA influences on the electromotility response. These results suggest that both ACh and GABA can change the electromotile activity of OHCs, in a tonotopically biased manner. ACh challenge evokes greater magnitude responses in basal turn OHCs, whereas GABA induces greater motility response decrease in apical turn OHCs. The control of the gain and magnitude of electromotility by the transmitter substances appear to involve at least two mechanisms. One is probably related to conformational changes of the voltage-to-movement converter molecules and a change in their number in an effective operational pool, the other operates via changing the electrical resistance of the basolateral cell membrane.