Rat Nicotinic Acetylcholine Receptor Alpha2beta2 Channels: Comparison of Functional Properties with Alpha4beta2 Channels in Xenopus Oocytes

Rat hippocampal interneurons express diverse subtypes of nicotinic acetylcholine receptors (nAChRs), including alpha7- and non-alpha7-containing receptors. Although the major subtype of non-alpha7 nAChRs in the hippocampus is thought to be composed of alpha4beta2 subunits, the molecular makeup of these non-alpha7 receptors is likely to be more complicated. Previously, we reported a high level of expression of the alpha2 nAChR subunit in individual rat hippocampal CA1 stratum oriens interneurons. In addition, the non-alpha7 nAChRs from these neurons are less sensitive to block by dihydro-beta-erythroidine (DHbetaE; the broad spectrum non-alpha7 nAChR antagonist) than that expected for alpha4beta2 receptors. We studied the functional properties of rat alpha2beta2 channels expressed in Xenopus oocytes using two-electrode voltage-clamp, and compared these to those properties of the more widely expressed and studied alpha4beta2 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. DHbetaE blocked both receptor subtypes, although the sensitivity to block of alpha4beta2 channels was significantly higher than that for alpha2beta2. Finally, the current-voltage (I-V) relationship for the alpha2beta2 channels more strongly rectified than for the alpha4beta2 channels. These data suggest that functional properties, in particular the sensitivity to block by DHbetaE, might be useful indicators to differentiate between native alpha4beta2 and alpha2beta2 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 alpha and beta subunits might be a general property of the heteromeric non-alpha7 nAChRs. By comparing the properties of expressed nAChRs with those of the native channels, we might be able to learn what role alpha2-containing nAChRs may be playing in forming functional channels in the hippocampus.