Rat nicotinic acetylcholine receptor α2β2 channels: comparison of functional properties with α4β2 channels in Xenopus oocytes

Abstract

Rat hippocampal interneurons express diverse subtypes of nicotinic acetylcholine receptors (nAChRs), including α7- and non-α7-containing receptors. Although the major subtype of non-α7 nAChRs in the hippocampus is thought to be composed of α4β2 subunits, the molecular makeup of these non-α7 receptors is likely to be more complicated. Previously, we reported a high level of expression of the α2 nAChR subunit in individual rat hippocampal CA1 stratum oriens interneurons. In addition, the non-α7 nAChRs from these neurons are less sensitive to block by dihydro-β-erythroidine (DHβE; the broad spectrum non-α7 nAChR antagonist) than that expected for α4β2 receptors. We studied the functional properties of rat α2β2 channels expressed in Xenopus oocytes using two-electrode voltage-clamp, and compared these to those properties of the more widely expressed and studied α4β2 channels. Dose-response curves for both receptor subtypes indicated that there are at least two different affinity sites for ACh, the fractional contribution of which depended on the ratio of injected RNA. DHβE blocked both receptor subtypes, although the sensitivity to block of α4β2 channels was significantly higher than that for α2β2. Finally, the current-voltage (I–V) relationship for the α2β2 channels more strongly rectified than for the α4β2 channels. These data suggest that functional properties, in particular the sensitivity to block by DHβE, might be useful indicators to differentiate between native α4β2 and α2β2 channels. In addition, these data suggest that the relative balance between the high- and low-affinity components being determined by the relative levels of the α and β subunits might be a general property of the heteromeric non-α7 nAChRs. By comparing the properties of expressed nAChRs with those of the native channels, we might be able to learn what role α2-containing nAChRs may be playing in forming functional channels in the hippocampus.