Single-channel currents of rat neuronal nicotinic acetylcholine receptors expressed in xenopus oocytes

Papke, Roger L.; Boulter, Jim; Patrick, Jim; Heinemann, Sabine

doi:10.1016/0896-6273(89)90269-9

Cited by 181 publications

(113 citation statements)

References 26 publications

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“…Expression in oocytes has revealed that α2 nAChR subunits form functional heteromeric receptors in combination with either β2 or β4 subunits (Papke et al, 1989). Given the spatial and temporal expression pattern of α2 mRNA in comparison to either β2 or β4 (Winzer-Serhan and Leslie, 1997, Zoli et al 1995, and the lack of co-detection in single cells of α2 and β4 by single cell RT-PCR (Sudweeks and Yakel, 2000), it seems likely that β2 rather than β4 will coassemble with α2 in adult and developing interneurons.…”

Section: Subunit Compositionmentioning

confidence: 99%

“…However, pharmacological and physiological analysis has revealed that α2β2 nAChRs have a relatively high affinity for nicotine and acetylcholine similar to α4β2, but have longer open time, greater peak conductance and current, and slower desensitization kinetics (Khiroug et al, 2004, Papke et al, 1989, Sudweeks and Yakel, 2000. These subtle pharmacological and electrophysiological differences can be important in tailoring the response to a cholinergic stimulus in specific cells within the diverse population of GABAergic interneurons.…”

Section: Subunit Compositionmentioning

confidence: 99%

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Postnatal expression of α2 nicotinic acetylcholine receptor subunit mRNA in developing cortex and hippocampus

Son

Winzer‐Serhan

2006

Journal of Chemical Neuroanatomy

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Nicotinic acetylcholine receptors (nAChRs) are pentameric ligand-gated cation channels composed of α and β subunits. nAChR subunit expression is highly regulated during development. Previous studies have revealed increased expression of α3, α5, α7, and β4 subunit mRNAs and α7 binding sites during hippocampal and cortical development. Here, we examined the expression of α2 subunit mRNA in rat cortex and hippocampus using highly sensitive radioactive in situ hybridization. α2 subunit mRNA expression was first detected at P3 in cortex and hippocampus. During postnatal development the distribution of α2 subunit mRNA expression was spatially similar to the one found in adult, exhibiting highly restricted expression in scattered cells mostly in cortical layer V and retrosplenial cortex, and in scattered cells in CA1/CA3 stratum oriens and CA3 stratum radiatum. However, the expression intensity and number of α2 positive cells strongly increased to reach peak levels in both cortex and hippocampus at P7 and decreased thereafter to moderate to low to levels. Double in situ hybridization revealed that most, but not all, α2 mRNA expression was located in nonpyramidal GAD-positive cortical and hippocampal interneurons. Thus, similar to other nAChR subunits, α2 mRNA expression is transiently upregulated during postnatal development and nAChRs containing α2 subunits could regulate GABAergic activity during a critical period of network formation.

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Section: Subunit Compositionmentioning

confidence: 99%

Section: Subunit Compositionmentioning

confidence: 99%

Postnatal expression of α2 nicotinic acetylcholine receptor subunit mRNA in developing cortex and hippocampus

Son

Winzer‐Serhan

2006

Journal of Chemical Neuroanatomy

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“…The subunit composition of nAChRs, expressed in Xenopus laevis oocytes, has profound effects on biophysical (channel open time, ion conductance, desensitization rates) and pharmacological (sensitivity to agonists and antagonists) properties of nAChRs [31,32,96]. These findings have prompted several research groups, including ours, to develop biochemical methods that might be used to characterize the functional properties of native nAChRs.…”

mentioning

confidence: 99%

The subtypes of nicotinic acetylcholine receptors on dopaminergic terminals of mouse striatum

Grady

Salminen

Laverty

et al. 2007

Biochemical Pharmacology

227

217

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This review summarizes studies that attempted to determine the subtypes of nicotinic acetylcholine receptors (nAChR) expressed in the dopaminergic nerve terminals in the mouse. A variety of experimental approaches has been necessary to reach current knowledge of these subtypes, including in situ hybridization, agonist and antagonist binding, function measured by neurotransmitter release from synaptosomal preparations, and immunoprecipitation by selective antibodies. Early developments that facilitated this effort include the radioactive labeling of selective binding agents, such as [ 125 I]-α-bungarotoxin and [ 3 H]-nicotine, advances in cloning the subunits, and expression and evaluation of function of combinations of subunits in Xenopus oocytes. The discovery of epibatidine and α-conotoxin MII (α-CtxMII), and the development of nAChR subunit null mutant mice have been invaluable in determining which nAChR subunits are important for expression and function in mice, as well as allowing validation of the specificity of subunit specific antibodies. These approaches have identified five nAChR subtypes of nAChR that are expressed on dopaminergic nerve terminals. Three of these contain the α6 subunit (α4α6β2β3, α6β2β3, α6β2) and bind α-CtxMII with high affinity. One of these three subtypes (α4α6β2β3) also has the highest sensitivity to nicotine of any native nAChR that has been studied, to date. The two subtypes that do not have high affinity for α-CtxMII (α4β2, α4α5β2) are somewhat more numerous than the α6* subtypes, but do bind nicotine with high affinity. Given that our first studies detected readily measured differences in sensitivity to agonists and antagonists among these five nAChR subtypes, it seems likely that subtype selective compounds could be developed that would allow therapeutic manipulation of diverse nAChRs that have been implicated in a number of human conditions. Alterations in nicotinic cholinergic receptor (nAChRs) number or function have been implicated in psychopathologies such as anxiety, attention deficit hyperactivity disorder, depression, schizophrenia (reviewed in [1,2,3]), at least one form of familial epilepsy [4], and Parkinson's and Alzheimer's diseases [5]. It is not particularly surprising that nAChRs might play important roles in modulating several human diseases given that binding sites for nicotinic ligands such as [ 125 I]-α-bungarotoxin [6,7,8], [ 3 H]-nicotine [7,8] Corresponding author: Sharon R Grady e-mail: sharon.grady@colorado.edu phone: 303-492-9677 fax: 303-492-8063 mailing address: Institute for Behavioral Genetics University of Colorado 447UCB Boulder, CO 80309. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered w...

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“…Because various combinations of these subunits have been shown to form functional non-␣7 nicotinic receptors (Papke et al, 1989;Boulter et al, 1990;Papke, 1993;Ramirez-Latorre et al, 1996), single-cell RT-PCR was used to determine which of these subunits were expressed in 17 interneurons that responded to DMPP. Consistent with the pharmacological data, single-cell RT-PCR analysis indicated that most of the interneurons that were excited by nicotinic agonists expressed the mRNAs for ␣4, ␣5, and ␤2 (Fig.…”

Section: Nicotinic Receptors Subunits Expressed By Responsive Internementioning

confidence: 99%

Selective Excitation of Subtypes of Neocortical Interneurons by Nicotinic Receptors

et al. 1999

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The cellular mechanisms by which neuronal nicotinic cholinergic receptors influence many aspects of physiology and pathology in the neocortex remain primarily unknown. Whole-cell recordings and single-cell reverse transcription (RT)-PCR were combined to analyze the effect of nicotinic receptor agonists on different types of neurons in acute slices of rat neocortex. Nicotinic receptor agonists had no effect on pyramidal neurons and on most types of interneurons, including parvalbuminexpressing fast spiking interneurons and somatostatinexpressing interneurons, but selectively excited a subpopulation of interneurons coexpressing the neuropeptides vasoactive intestinal peptide (VIP) and cholecystokinin. This excitation persisted in the presence of glutamate, GABA, and muscarinic receptor antagonists and in the presence of tetrodotoxin and low extracellular calcium, suggesting that the depolarization was mediated through the direct activation of postsynaptic nicotinic receptors. The responses were blocked by the nicotinic receptor antagonists dihydro-␤-erythroidine and mecamylamine and persisted in the presence of the ␣7 selective nicotinic receptor antagonist methyllycaconitine, suggesting that the involved nicotinic receptors lacked the ␣7 subunit. Single-cell RT-PCR analysis indicated that the majority of the interneurons that responded to nicotinic stimulation coexpressed the ␣4, ␣5, and ␤2 nicotinic receptor subunits. Therefore, these results provide a role for non-␣7 nicotinic receptors in the selective excitation of a subpopulation of neocortical interneurons. Because the neocortical interneurons expressing VIP have been proposed previously to regulate regional cortical blood flow and metabolism, these results also provide a cellular basis for the neuronal regulation of cortical blood flow mediated by acetylcholine. Key words: single-cell PCR; neuropeptides; calcium-binding proteins; methyllycaconitine; dihydro-␤-erythroidine; acetylcholine; mecamylamineNicotinic receptors are implicated in many important f unctions of the mammalian neocortex, including memory formation (Granon et al., 1995) and neuronal regulation of regional cerebral blood flow (Gitelman and Prohovnik, 1992;Uchida et al., 1997), as well as cortical pathologies such as Alzheimer's disease (Whitehouse et al., 1988;Newhouse et al., 1997), epilepsy (Steinlein et al., 1995, and Tourette's syndrome (Sanberg et al., 1997(Sanberg et al., , 1998. The cellular basis for the effects of nicotinic receptor stimulation is currently unknown but lies within its effects on the complex interactions between the excitatory glutamatergic pyramidal neurons and the inhibitory interneurons.A variety of different neuronal nicotinic receptor subunits have been cloned and named ␣2-␣9 and ␤2-␤4 (Elgoyhen et al., 1994;Le Novere and Changeux, 1995). C lassically, two broad subfamilies of nicotinic receptors have been characterized in neurons according to their sensitivity to ␣-bungarotoxin. Subunits ␣7 and ␣8 form a family of ␣-bungarotoxin-sensitive channels (Couturier...

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Single-channel currents of rat neuronal nicotinic acetylcholine receptors expressed in xenopus oocytes

Cited by 181 publications

References 26 publications

Postnatal expression of α2 nicotinic acetylcholine receptor subunit mRNA in developing cortex and hippocampus

Postnatal expression of α2 nicotinic acetylcholine receptor subunit mRNA in developing cortex and hippocampus

The subtypes of nicotinic acetylcholine receptors on dopaminergic terminals of mouse striatum

Selective Excitation of Subtypes of Neocortical Interneurons by Nicotinic Receptors

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