Conductance Properties of the Acetylcholine Receptor Current of Guinea Pig Outer Hair Cells

The nicotinic acetylcholine receptor (AChR) current of outer hair cells (OHCs) was investigated in isolated and voltage-clamped cells under conditions where co-activating Ca(2+)-activated K(+) currents had been abolished using internal BAPTA, external calcium removal and/or depolarisation to positive voltages. The AChR current activated rapidly and thereafter declined in the continued presence of ACh. Reversal potential measurements indicated that it was a non-specific cation current with a substantial Ca(2+) permeability. It had a characteristic bidirectional rectification with an especially prominent outward component in solutions containing 1 mM Ca(2+). The I-V relation was fitted with a single-energy barrier model. The fit suggests a blocking site within the channel, situated about one third of the way through the membrane from the outside and probably normally occupied by Ca(2+) or Mg(2+). The AChR current was sensitive to the external Ca(2+) since it was reduced, to differing extents, in nominally Ca(2+)-free saline or in high Ca(2+) saline (10 mM). In the presence of a nominally Mg(2+)-free solution containing 0.4 mM Ca(2+), the currents were larger, indicating a potentiated response. This type of behaviour is also shown by recombinant alpha 9 alpha 10 AChRs, suggesting a close similarity. The AChR current at both positive and negative voltages was reduced in external solutions where most of the Na(+) had been replaced by NMG(+). The conductance properties of the OHC AChR are compared with alpha 9 alpha 10 receptors and nicotinic receptors in other hair cells and discussed in terms of the accepted functional role of providing calcium influx leading to efferent synaptic inhibition of hair cells.