Skip to main content
SpringerLink
Log in

Desensitization of α7 nicotinic receptors potentiated the inhibitory effect on M-current induced by stimulation of muscarinic receptors in rat superior cervical ganglion neurons

  • Published:
Journal of Neural Transmission Aims and scope Submit manuscript

Summary.

Whole-cell patch-clamp recording from rat superior cervical ganglion neurons in culture was used to investigate the modulatory effect of desensitized α7-nAChRs on mAChRs. An inward α-bungarotoxin and methyllycaconitine sensitive current was elicited by rapid application of choline, which consisted of a fast and a slow desensitizing component. The amplitude of choline-evoked currents recorded 0.5, 1, 2, and 3 min after the prolonged application of choline (10 mM, 30 s) decreased to 25.3 ± 9.2%, 45.9 ± 11.8%, 66.3 ± 14.5%, and 73.9 ± 13.3% of their baseline levels, respectively. The amplitudes of M-currents, recorded at the same time intervals after the similar prolonged stimulation with choline, were decreased to 52.7 ± 17.4%, 63.9 ± 4.2%, 70.9 ± 2.8%, and 72.9 ± 17.3% of initial values respectively by focal application of pilocarpine (1 mM, 5 s) onto the soma of neurons. By contrast, before the desensitization of α7-nAChRs, M-currents were only decreased to 79.8 ± 13.7% of baseline levels by pilocarpine (1 mM, 5 s). Whereas the desensitization of α7-nAChRs had no direct effects on M-currents, and the facilitated effects on muscarinic agonists on the M-currents induced by desensitized α7-nAChRs, were removed in the presence of α-bungarotoxin and methyllycaconitine. These results indicated that desensitization of α7-nAChRs could potentiate the inhibitory effect on M-current by stimulation of mAChRs with their agonist.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • SP Aiken BJ Lampe PA Murphy BS Brown (1995) ArticleTitleReduction of spike frequency adaptation and blockade of M-current in rat CA1 pyramidal neurons by linopirdine (Dup 996), a neurotransmitter release enhancer. Br J Pharmacol 115 1163–1168 Occurrence Handle7582539

    PubMed  Google Scholar 

  • M Alkondon EF Pereira WS Cortes A Maelicke EX Albuquerque (1997) ArticleTitleCholine is a selective agonist of alpha7 nicotinic acetylcholine receptors in the rat brain neurons. Eur J Neurosci 9 2734–2742 Occurrence Handle9517478

    PubMed  Google Scholar 

  • R Anand L Bason MS Saedi V Gerzanich X Peng J Lindstrom (1993) ArticleTitleReporter epitopes: a novel approach to examine transmembrane topology of integral membrane proteins applied to the alpha 1 subunit of the nicotinic acetylcholine receptor. Biochemistry 32 9975–9984 Occurrence Handle10.1021/bi00089a013 Occurrence Handle7691173

    Article  PubMed  Google Scholar 

  • F Berger FH Gage S Vijayaraghavan (1998) ArticleTitleNicotinic receptor-induced apoptotic cell death of hippocampal progenitor cells. J Neurosci 18 6871–6881 Occurrence Handle9712657

    PubMed  Google Scholar 

  • L Bernheim A Mathie B Hille (1992) ArticleTitleCharacterization of muscarinic receptor subtypes inhibiting Ca2+ current and M current in rat sympathetic neurons. Proc Natl Acad Sci USA 89 9544–9548 Occurrence Handle1329101

    PubMed  Google Scholar 

  • DA Brown PR Adams (1980) ArticleTitleMuscarinic suppression of a novel voltage-sensitive K+ current in a vertebrate neuron. Nature 283 673–676 Occurrence Handle10.1038/283673a0 Occurrence Handle6965523

    Article  PubMed  Google Scholar 

  • EN Brown JJ Galligan (2003) ArticleTitleMuscarinic receptors couple to modulation of nicotinic ACh receptor desensitization in myenteric neurons. Am J Physiol Gastrointest Liver Physiol 285 G37–G44 Occurrence Handle12620888

    PubMed  Google Scholar 

  • B Buisson D Bertrand (1998) ArticleTitleAllosteric modulation of neuronal nicotinic acetylcholine receptors. J Physiol (Paris) 92 89–100 Occurrence Handle10.1016/S0928-4257(98)80144-7

    Article  Google Scholar 

  • K Chang DK Berg (1999) ArticleTitleDependence of circuit function on nicotinic acetylcholine receptor containing α7 subunits. J Neurosci 19 3701–3710 Occurrence Handle10234002

    PubMed  Google Scholar 

  • JP Changeux A Devillers-Thiery P Chemouilli (1984) ArticleTitleAcetylcholine receptor: an allosteric protein. Science 225 1335–1345 Occurrence Handle6382611

    PubMed  Google Scholar 

  • WG Conroy DK Berg (1998) ArticleTitleNicotinic receptor subtypes in the developing chick brain: appearance of a species containing the alpha4, beta2, and alpha5 gene products. Mol Pharmacol 53 392–401 Occurrence Handle9495803

    PubMed  Google Scholar 

  • A Constanti JA Sim (1987) ArticleTitleMuscarinic receptors mediating suppression of the M-current in guinea-pig olfactory cortex neurones may be of the m2-subtype. Br J Pharmacol 90 3–5 Occurrence Handle3814922

    PubMed  Google Scholar 

  • PJ Corringer S Bertrand S Bohler SJ Edelstein JP Changeux D Bertrand (1998) ArticleTitleCritical elements determining diversity in agonist binding and desensitization of neuronalnicotinic acetylcholine receptors. J Neurosci 18 648–657 Occurrence Handle9425007

    PubMed  Google Scholar 

  • S Couturier D Bertrand JM Matter MC Hernandez S Bertrand N Millar S Valera T Barkas M Ballivet (1990) ArticleTitleA neuronal nicotinic acetylcholine receptor subunit (alpha7) is developmentally regulated and forms a homoligomeric channel blocked by alpha-BTX. Neuron 5 847–856 Occurrence Handle10.1016/0896-6273(90)90344-F Occurrence Handle1702646

    Article  PubMed  Google Scholar 

  • J Cuevas AL Roth DK Berg (2000) ArticleTitleTwo distinct classes of functional α7-containing nicotinic receptor on rat superior cervical ganglion neurons. J Physiol 525 735–746 Occurrence Handle10.1111/j.1469-7793.2000.t01-1-00735.x Occurrence Handle10856125

    Article  PubMed  Google Scholar 

  • A Drasdo M Caufield D Bertrand S Bertrand S Wonnacott (1992) ArticleTitleMethyllycaconitine: a novel nicotinic antagonist. Mol Cell Neurosci 3 237–243 Occurrence Handle10.1016/1044-7431(92)90043-2

    Article  Google Scholar 

  • CP Fenster ML Beckman JC Parker EB Sheffield TL Whitworth MW Quick RA Lester (1999) ArticleTitleRegulation of alpha4beta2 nicotinic receptor desensitization by calcium and protein kinase C. Mol Pharmacol 55 432–443 Occurrence Handle10051526

    PubMed  Google Scholar 

  • CH Franke H Parnas G Hovav J Dudel (1993) ArticleTitleA molecular scheme for the reaction between acetylcholine and nicotinic channels. Biophys J 64 339–356 Occurrence Handle7681332

    PubMed  Google Scholar 

  • S Fujii Z Ji K Sumikawa (2000) ArticleTitleInactivation of α7 ACh receptors and activation of non-α7 ACh receptors both contribute to long term potentiation induction in the hippocampal CA1 region. Neurosci Lett 286 134–138 Occurrence Handle10.1016/S0304-3940(00)01076-4 Occurrence Handle10825655

    Article  PubMed  Google Scholar 

  • R Gray AS Rajan KA Radcliffe M Yakehiro JA Dani (1996) ArticleTitleHippocampal synaptic transmission enhanced by low concentrations of nicotine. Nature 383 713–716 Occurrence Handle10.1038/383713a0 Occurrence Handle8878480

    Article  PubMed  Google Scholar 

  • J Guo GG Schofield (2003) ArticleTitleActivation of muscarinic m5 receptors inhibits recombinant KCNQ2/KCNQ3 K+ channels expressed in HEK293T cells. Eur J Pharmacol 462 25–32 Occurrence Handle10.1016/S0014-2999(03)01323-2 Occurrence Handle12591092

    Article  PubMed  Google Scholar 

  • SE Hamilton MD Loose M Qi AI Levey B Hille GS McKnight RL Idzerda NM Nathanson (1997) ArticleTitleDisruption of the m1 receptor gene ablates muscarinic receptor-dependent M current regulation and seizure activity in mice. Proc Natl Acad Sci USA 94 13311–13316 Occurrence Handle10.1073/pnas.94.24.13311 Occurrence Handle9371842

    Article  PubMed  Google Scholar 

  • S Hefft S Hulo D Bertrand D Muller (1999) ArticleTitleSynaptic transmission at nicotinic acetylcholine receptors in rat hippocampal organotypic cultures and slices. J Physiol 515 769–776 Occurrence Handle10.1111/j.1469-7793.1999.769ab.x Occurrence Handle10066903

    Article  PubMed  Google Scholar 

  • SA Helekar D Char S Neff J Patrick (1994) ArticleTitleProlyl isomerase requirement for the expression of functional homoligomeric ligand-gated ion channels. Neuron 71 1–10

    Google Scholar 

  • MM Hosey (1992) ArticleTitleDiversity of structure, signaling and regulation within the family of muscarinic cholinergic receptors. FASEB J 6 845–852 Occurrence Handle1740234

    PubMed  Google Scholar 

  • SS Khiroug PC Harkness PW Lamb SN Sudweeks L Khiroug NS Millar JL Yakel (2002) ArticleTitleRat nicotinic ACh receptor alpha7 and beta2 subunits co-assemble to form functional heteromeric nicotinic receptor channels. J Physiol 540 425–434 Occurrence Handle10.1113/jphysiol.2001.013847 Occurrence Handle11956333

    Article  PubMed  Google Scholar 

  • F Kimura (2000) ArticleTitleCholinergic modulation of cortical function: a hypothetical role in shifting the dynamics in cortical network. Neurosci Res 38 19–26 Occurrence Handle10.1016/S0168-0102(00)00151-6 Occurrence Handle10997574

    Article  PubMed  Google Scholar 

  • PM Lippiello SB Sears KG Fernandes (1987) ArticleTitleKinetics and mechanism of L-[3H] nicotine binding to putative high affinity receptor sites in rat brain. Mol Pharmacol 31 392–400 Occurrence Handle3574288

    PubMed  Google Scholar 

  • A Mandelzys P DeKoninck E Cooper (1995) ArticleTitleAgonist and toxin sensitivities of ACh-evoked currents on neurones expressing multiple nicotinic ACh receptor subunits. J Neurophysiol 74 1212–1221 Occurrence Handle7500145

    PubMed  Google Scholar 

  • NV Marrion TG Smart SJ Marsh DA Brown (1989) ArticleTitleMuscarinic suppression of the M-current in the rat sympathetic ganglion is mediated by receptors of the M1 subtype. Br J Pharmacol 89 557–573

    Google Scholar 

  • EL Ochoa A Chattopadhyay MG McNamee (1989) ArticleTitleDesensitization of the nicotinic acetylcholine receptor: molecular mechanisms and effect of modulators. Cell Mol Neurobiol 9 141–178 Occurrence Handle10.1007/BF00713026 Occurrence Handle2663167

    Article  PubMed  Google Scholar 

  • E Palma L Maggi B Barabino F Eusebi M Ballivet (1999) ArticleTitleNicotinic acetylcholine receptors assembled from the α7 and β3 subunits. J Biol Chem 274 18335–18340 Occurrence Handle10.1074/jbc.274.26.18335 Occurrence Handle10373437

    Article  PubMed  Google Scholar 

  • RL Papke M Bencherif P Lippiello (1996) ArticleTitleAn evaluation of neuronalnicotinic acetylcholine receptor activation by quaternary nitrogen compounds indicates that choline is selective for the a7 subtype. Neurosci Lett 213 201–204 Occurrence Handle8873149

    PubMed  Google Scholar 

  • BS Qiu CH Cho SCG Hui CW Ogle (1992) ArticleTitleChronic nicotine intake increases the responses to muscarinic receptor stimulation. Pharmacology 44 41–47

    Google Scholar 

  • N Quinson JP Miolan JP Niel (2000) ArticleTitleMuscarinic receptor activation is a prerequisite for the endogenous release of nitric oxide modulating nicotinic transmission within the coeliac ganglion in the rabbit. Neuroscience 95 1129–1138 Occurrence Handle10.1016/S0306-4522(99)00518-7 Occurrence Handle10682720

    Article  PubMed  Google Scholar 

  • J Robbins MP Caulfield H Higashida DA Brown (1991) ArticleTitleGenotypic m3-muscarinic receptors preferentially inhibit M-currents in DNA-transfected NG108-15 neuroblastoma × glioma hybrid cells. Eur J Neurosci 3 820–824 Occurrence Handle12106468

    PubMed  Google Scholar 

  • ST Rouse SE Hamilton LT Potter NM Nathanson PJ Conn (2000) ArticleTitleMuscarinic-induced modulation of potassium conductances is unchanged in mouse hippocampal pyramidal cells that lack functional M1 receptors. Neurosci Lett 278 61–64 Occurrence Handle10.1016/S0304-3940(99)00914-3 Occurrence Handle10643801

    Article  PubMed  Google Scholar 

  • M Saito C Nelson L Salkoff CJ Lingle (1997) ArticleTitleA cysteine-rich domain defined by a novel exon in a slovariant in rat adrenal chromaffin cells and PC12 cells. J Biol Chem 272 11710–11717 Occurrence Handle10.1074/jbc.272.18.11710 Occurrence Handle9115223

    Article  PubMed  Google Scholar 

  • R Schoepfer WG Conroy P Whiting M Gore J Lindstrom (1990) ArticleTitleBrain alpha-bungarotoxin binding protein cDNAs and MAbs reveal subtypes of this branch of the ligand-gated ion channel gene superfamily. Neuron 5 35–48 Occurrence Handle10.1016/0896-6273(90)90031-A Occurrence Handle2369519

    Article  PubMed  Google Scholar 

  • R Seddic A Bradaia J Trouslard (2003) ArticleTitleCholine induces Ca2+ entry in cultured sympathetic neurons isolated from rat superior cervical ganglion. Eur J Pharmacol 471 165–176 Occurrence Handle10.1016/S0014-2999(03)01860-0 Occurrence Handle12826235

    Article  PubMed  Google Scholar 

  • MS Shapiro J Gomeza SE Hamilton B Hille MD Loose NM Nathanson JP Roche J Wess (2001) ArticleTitleIdentification of subtypes of muscarinic receptors that regulate Ca2+ and K+ channel activity in sympathetic neurons. Life Sci 68 2481–2487 Occurrence Handle10.1016/S0024-3205(01)01042-6 Occurrence Handle11392616

    Article  PubMed  Google Scholar 

  • MJ Shipston RR Duncan AG Clark FA Antoni L Tian (1999) ArticleTitleMolecular components of large conductance calcium-activated potassium (BK) channels in mouse pituitary corticotropes. Mol Endocrinol 13 1728–1737 Occurrence Handle10.1210/me.13.10.1728 Occurrence Handle10517674

    Article  PubMed  Google Scholar 

  • MV Skok LP Voitenko SV Voitenko EY Lykhmus EN Kalashnik TI Litvin SJ Tzartos VI Skok (1999) ArticleTitleAlpha subunit composition of nicotinic acetylcholine receptors in the rat autonomic ganglia neurons as determined with subunit-specific anti-alpha (181–192) peptide antibodies. Neuroscience 93 1427–1436 Occurrence Handle10.1016/S0306-4522(99)00160-8 Occurrence Handle10501468

    Article  PubMed  Google Scholar 

  • L Toro M Wallner P Meera Y Tanaka (1998) ArticleTitleMaxi-K(Ca), a unique member of the voltage-gated K channel superfamily. News Physiol Sci 13 112–117 Occurrence Handle11390773

    PubMed  Google Scholar 

  • KE Vogt WG Regehr (2001) ArticleTitleCholinergic modulation of excitatory synaptic transmission in the CA3 area of the hippocampus. J Neurosci 21 75–83 Occurrence Handle11150322

    PubMed  Google Scholar 

  • LP Voitenko SV Voitenko MV Skok HE Purnyn VI Skok (2001) ArticleTitleNicotinic acetylcholine receptor subtypes in rat superior cervical ganglion neurons as studied by sequential application of two alpha-subunit-specific antibodies. Neurosci Lett 303 37–40 Occurrence Handle10.1016/S0304-3940(01)01705-0 Occurrence Handle11297818

    Article  PubMed  Google Scholar 

  • Q Wan ZP Luo H Wang (2003) ArticleTitleMuscarinic receptor activities potentiated by desensitization of nicotinic receptors in rat superior cervical ganglia. Acta Pharmacol Sin 24 657–662 Occurrence Handle12852831

    PubMed  Google Scholar 

  • H Wang (1997) ArticleTitleModulation by nicotine on muscarinic receptor-effector systems. Acta Pharmacol Sin 18 193–197

    Google Scholar 

  • H Wang WY Cui CG Liu (1994) ArticleTitleModulatory effects of nicotine on acetylcholine-induced guinea pig ileum contraction. Chin J Appl Physiol 10 102–104

    Google Scholar 

  • H Wang WY Cui CG Liu (1995) ArticleTitleModulatory effects of nicotine on oxotremorine and arecoline-induced salivation in mice. Chin J Appl Physiol 11 109–112

    Google Scholar 

  • H Wang WY Cui CG Liu (1995) ArticleTitleModulatory effects of nicotine on carbachol induced bradycardia and hypotention. Chin J Appl Physiol 11 330–332

    Google Scholar 

  • H Wang WY Cui CG Liu (1996) ArticleTitleCharacteristics of behavioral and electroencephalogram convulsions induced by nicotine and its di(+) tartrate. Chin J Pharmacol Toxicol 10 169–172

    Google Scholar 

  • H Wang WY Cui CG Liu (1996) ArticleTitleModulation of nicotine on muscarinic agonist-depressed spontaneous locomotor activity. Chin J Pharmacol Toxicol 10 98–100

    Google Scholar 

  • H Wang WY Cui CG Liu (1996) ArticleTitleRegulatory effects of acutely repeated nicotine treatment towards central muscarinic receptors. Life Sci 59 1415–1421 Occurrence Handle10.1016/0024-3205(96)00469-9 Occurrence Handle8890920

    Article  PubMed  Google Scholar 

  • H Wang WY Cui HZ Bu CG Liu (1996) ArticleTitleEffects of arecoline on myo-inositol level of rat brain and nicotine modulation. Bull Acad Mil Med Sci 20 165–167

    Google Scholar 

  • H Wang WY Cui CG Liu (1997) ArticleTitleRegulatory effects of chronically repeated nicotine treatment towards the functions of central muscarinic receptors. Chin J Pharmacol Toxicol 11 3–6

    Google Scholar 

  • Y Zhou WM Schopperle H Murrey A Jaramillo D Dagan LC Griffith IB Levitan (1999) ArticleTitleA dynamically regulated 14-3-3, Slob, and Slowpoke potassium channel complex in Drosophila presynaptic nerve terminals. Neuron 22 809–818 Occurrence Handle10.1016/S0896-6273(00)80739-4 Occurrence Handle10230800

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Beijing Institute of Pharmacology and Toxicology, Beijing, Nanjing, China

    X. Yin, W. Cui & H. Wang

  2. Department of Pharmacology and Neurobiology, Nanjing Medical University, Nanjing, China

    X. Yin & G. Hu

Authors
  1. X. Yin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. W. Cui
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. G. Hu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. H. Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Yin, X., Cui, W., Hu, G. et al. Desensitization of α7 nicotinic receptors potentiated the inhibitory effect on M-current induced by stimulation of muscarinic receptors in rat superior cervical ganglion neurons. J Neural Transm 112, 1133–1148 (2005). https://doi.org/10.1007/s00702-004-0260-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00702-004-0260-6

Search

Navigation