Unraveling the evolutionary history of nicotinic acetylcholine receptor subunits

IRINA MARCOVICH; MARCELA LIPOVSEK; ANABELLA TRIGILA; LUCIA FRANCHINI; PAOLA PLAZAS; ANA BELÉN ELGOYHEN

Congreso; Neuroscience 2017; 2017

Society for Neuroscience

The pentameric ligand-gated ion channels superfamily comprises a number of receptors which includes the nicotinic acetylcholine receptors (nAChRs). These are expressed in the central and peripheral nervous system, the neuromuscular end-plate and the auditory epithelium. Neuronal nAChRs can assemble from a variety of subunits: α2- α8 and β2- β4; whereas the inner ear hair cells nAChRs only assemble from α9 and α10 subunits. The α9α10 nAChR exhibits peculiar characteristics that distinguish it from the rest of the nAChRs. For instance, in contrast to all nAChRs that serve excitatory neurotransmission, the activation of α9α10 nAChRs produces hyperpolarization of the postsynaptic cell, since it is coupled to small conductance calcium-dependent potassium channels. Previous work has determined that mammalian α10, but not other nAChRs subunits, has been under positive darwinian selection and acquired several non-synonymous substitutions in the coding region (Franchini and Elgoyhen, 2006). This is accompanied by differences in calcium permeability of α9α10 receptors across vertebrate species (Lipovsek, et al. 2012). Given that α9α10 is the only nAChR expressed in inner ear hair cells, we propose that these acquired amino acid changes in the primary sequence of the α10 subunit are the basis for functional diversity across species in the case of α9α10. On the contrary, neuronal nAChRs can achieve differential channel properties by assembling from the wide variety of subunits expressed in the brain. Therefore, we hypothesize that 1- the biophysical properties of the α9α10 nAChRs should vary across different vertebrate species, but those of neuronal nAChRs should be conserved and 2- the expression pattern of neuronal nAChRs should vary across vertebrate species. We conducted a comparative analysis of the biophysical properties of recombinant rat (mammalian), chicken (avian) and frog (amphibian) α9α10, α7 and α4β2 receptors expressed in Xenopus laevis oocytes. α9α10 nAChRs from the three species present striking differences in their desensitization rate, calcium permeability and modulation and current-voltage curves. In contrast, in the case of neuronal receptors these properties are conserved when comparing rat, chicken and frog receptors. These results suggest that the differential functional properties of the α9α10 nAChRs across species resulted from the peculiar evolutionary process to which mammalian α10 was subjected. In the case of neuronal nAChRs subunits, the acquisition of differential channel properties might be achieved by differences in subunit combinatorial assemblies across species.