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Publication : Molecular and physiological diversity of nicotinic acetylcholine receptors in the midbrain dopaminergic nuclei.

First Author  Klink R Year  2001
Journal  J Neurosci Volume  21
Issue  5 Pages  1452-63
PubMed ID  11222635 Mgi Jnum  J:109365
Mgi Id  MGI:3628837 Doi  10.1523/JNEUROSCI.21-05-01452.2001
Citation  Klink R, et al. (2001) Molecular and physiological diversity of nicotinic acetylcholine receptors in the midbrain dopaminergic nuclei. J Neurosci 21(5):1452-63
abstractText  Nicotinic acetylcholine receptors (nAChRs) on dopaminergic (DA) and GABAergic (Gaba) projection neurons of the substantia nigra (SN) and ventral tegmental area (VTA) are characterized by single-cell RT-PCR and patch-clamp recordings in slices of rat and wild-type, beta2-/-, alpha4-/-, and alpha7-/- mice. The eight nAChR subunits expressed in these nuclei, alpha3-7 and beta2-4, contribute to four different types of nAChR-mediated currents. Most DA neurons in the SN and VTA express two nAChR subtypes. One is inhibited by dihydro-beta-erythroidine (2 microm), alpha-conotoxin MII (10 nm), and methyllycaconitine (1 nm) but does not contain the alpha7 subunit; it possesses a putative alpha4alpha6alpha5(beta2)(2) composition. The other subtype is inhibited by dihydro-beta-erythroidine (2 microm) and has a putative alpha4alpha5(beta2)(2) composition. Gaba neurons in the VTA exhibit a third subtype with a putative (alpha4)(2)(beta2)(3) composition, whereas Gaba neurons in the SN have either the putative (alpha4)(2)(beta2)(3) oligomer or the putative alpha4alpha6alpha5(beta2)(2) oligomer. The fourth subtype, a putative (alpha7)(5) homomer, is encountered in less than half of DA and Gaba neurons, in the SN as well as in the VTA. Neurons in the DA nuclei thus exhibit a diversity of nAChRs that might differentially modulate reinforcement and motor behavior.
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