α10: A determinant of nicotinic cholinergic receptor function in mammalian vestibular and cochlear mechanosensory hair cells

Abstract

We report the cloning and characterization of rat ␣10, a previously unidentified member of the nicotinic acetylcholine receptor (nAChR) subunit gene family. The protein encoded by the ␣10 nAChR subunit gene is most similar to the rat ␣9 nAChR, and both ␣9 and ␣10 subunit genes are transcribed in adult rat mechanosensory hair cells. Injection of Xenopus laevis oocytes with ␣10 cRNA alone or in pairwise combinations with either ␣2-␣6 or ␤2-␤4 subunit cRNAs yielded no detectable ACh-gated currents. However, coinjection of ␣9 and ␣10 cRNAs resulted in the appearance of an unusual nAChR subtype. Compared with homomeric ␣9 channels, the ␣9␣10 nAChR subtype displays faster and more extensive agonist-mediated desensitization, a distinct currentvoltage relationship, and a biphasic response to changes in extracellular Ca 2؉ ions. The pharmacological profiles of homomeric ␣9 and heteromeric ␣9␣10 nAChRs are essentially indistinguishable and closely resemble those reported for endogenous cholinergic eceptors found in vertebrate hair cells. Our data suggest that efferent modulation of hair cell function occurs, at least in part, through heteromeric nAChRs assembled from both ␣9 and ␣10 subunits.

Desensitization of neuronal nicotinic receptors

“…The chick ␣8 subunit forms homomeric receptors that desensitize, at least in oocytes, with the same order of magnitude as ␣7 receptors but at much lower concentrations of nicotine or ACh Gotti et al, 1994). Both the rate and extent of desensitization of slowly/ nondesensitizing cochlear ␣9 homomeric receptors are enhanced when these subunits are expressed together with ␣10 subunits (Elgoyhen et al, 2001; but see Sgard et al, 2002).…”

Regulatory mechanisms that govern nicotinic synapse formation in neurons

“…Each individual nAChR channel is composed of five membrane-spanning subunits arranged to form a central ion channel pore. To date, 17 nAChR subunit genes have been cloned from vertebrates (Elgoyhen et al, 2001). This large multigene family encodes subunits of the neuronal and skeletal muscle type nAChRs.…”

Plasticity of the murine spleen T-cell cholinergic receptors and their role in in vitro differentiation of naïve CD4 T cells toward the Th1, Th2 and Th17 lineages

“…In other cells, 12 'neuronal' nAChR subunit genes encoding a pentameric protein have been identified and designated a2-a10 and b2-b4. [12][13][14][15] Each subunit has four putative transmembrane-spanning domains and a similar topological structure. The a7 and a9 subunits are capable of forming homomeric nAChR channels, which are a-bungarotoxin sensitive.…”

“…The heteromeric channels can be composed of a2, a3, a4, a5, a6, b2, b3 and b4 subunits, for example, a3(b2/b4)±a5 and also a9 can form a heteromeric channel with a10. 15 The mAChRs are single-subunit transmembrane glycoproteins that mediate the metabolic response to ACh through the interactions of G proteins with signal transducing enzymes, leading to increases or decreases in second messengers, ion concentrations and modulations of protein kinase activities. The mAChR family is comprised of five, M 1 -M 5 , G protein-coupled receptor subtypes.…”