A hybrid zone comprising staggered chromosomal clines in the house mouse ( Mus musculus domesticus )

Abstract

To gain insight into the activation mechanism of homomeric ligand-gated receptor-channels, we examined human homomeric $\rho _{1}$ GABA receptors with fewer than the normal number of agonist binding sites. This was accomplished by coexpressing different ratios of wild type and activation-impaired $\rho _{1}$ subunits. Dose-response relations from oocytes coexpressing wild type and mutant subunits were comprised of two components in terms of GABA sensitivity; one `wild type'-like and the other `mutant'-like. Applying the binomial hypothesis to subunit coassembly enabled us to correlate these two components of the GABA dose-response relations to the underlying chimaeric receptor subtypes. We demonstrate that the receptors activate near normal provided that they are comprised of at least three wild type subunits. Our data are consistent with five equivalent and independent GABA binding sites of which only three need bind GABA to open the pore. The two additional binding sites may increase the GABA sensitivity of the $\rho _{1}$ receptor and, when bound by agonist, stabilize the open state.