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Pflügers Archiv - European Journal of Physiology

, Volume 456, Issue 6, pp 1049–1060 | Cite as

Muscarinic ACh receptor-mediated control of thalamic activity via Gq/G11-family G-proteins

  • Tilman Broicher
  • Nina Wettschureck
  • Thomas Munsch
  • Philippe Coulon
  • Sven G. Meuth
  • Tatyana Kanyshkova
  • Thomas Seidenbecher
  • Stefan Offermanns
  • Hans-Christian Pape
  • Thomas BuddeEmail author
Cellular Neurophysiology

Abstract

A genetic knock out was used to determine the specific contribution of Gq/G11-family G-proteins to the function of thalamocortical relay (TC) neurons. Disruption of Gαq function in a conditional forebrain-specific Gαq/Gα11-double-deficient mouse line \(\left( {{{{\text{G $ \alpha $ }}_{\text{q}} } \mathord{\left/ {\vphantom {{{\text{G $ \alpha $ }}_{\text{q}} } {{\text{G $ \alpha $ }}_{11}^{{ - \mathord{\left/ {\vphantom { - - }} \right. \kern-\nulldelimiterspace} - }} }}} \right. \kern-\nulldelimiterspace} {{\text{G $ \alpha $ }}_{11}^{{ - \mathord{\left/ {\vphantom { - - }} \right. \kern-\nulldelimiterspace} - }} }}} \right)\) had no effects on the resting membrane potential (V rest) and the amplitude of the standing outward current (I SO). Stimulation of muscarinic acetylcholine (ACh) receptors (mAChR; muscarine, 50 μM) induced a decrease in I SO amplitude in wild-type mice (36 ± 4%, n = 5), a constitutive Gα11-deficient mouse line (\({\text{G $ \alpha $ }}_{11}^{{ - \mathord{\left/ {\vphantom { - - }} \right. \kern-\nulldelimiterspace} - }} \); 36 ± 3%, n = 8), and \({{{\text{G $ \alpha $ }}_{\text{q}} } \mathord{\left/ {\vphantom {{{\text{G $ \alpha $ }}_{\text{q}} } {{\text{G $ \alpha $ }}_{11}^{{ - \mathord{\left/ {\vphantom { - - }} \right. \kern-\nulldelimiterspace} - }} }}} \right. \kern-\nulldelimiterspace} {{\text{G $ \alpha $ }}_{11}^{{ - \mathord{\left/ {\vphantom { - - }} \right. \kern-\nulldelimiterspace} - }} }}\) (11 ± 2%, n = 16). Current-clamp recordings revealed a muscarine-induced positive shift in V rest of 23 ± 2 mV (n = 6), 18 ± 5 mV (n = 5), and 2 ± 1 mV (n = 9) in wild type, \({\text{G $ \alpha $ }}_{11}^{{ - \mathord{\left/ {\vphantom { - - }} \right. \kern-\nulldelimiterspace} - }} \), and \({{{\text{G $ \alpha $ }}_{\text{q}} } \mathord{\left/ {\vphantom {{{\text{G $ \alpha $ }}_{\text{q}} } {{\text{G $ \alpha $ }}_{11}^{{ - \mathord{\left/ {\vphantom { - - }} \right. \kern-\nulldelimiterspace} - }} }}} \right. \kern-\nulldelimiterspace} {{\text{G $ \alpha $ }}_{11}^{{ - \mathord{\left/ {\vphantom { - - }} \right. \kern-\nulldelimiterspace} - }} }}\), respectively. This depolarization was associated with a change in TC neuron activity from burst to tonic firing in wild type and \({\text{G $ \alpha $ }}_{11}^{{ - \mathord{\left/ {\vphantom { - - }} \right. \kern-\nulldelimiterspace} - }} \), but not in \({{{\text{G $ \alpha $ }}_{\text{q}} } \mathord{\left/ {\vphantom {{{\text{G $ \alpha $ }}_{\text{q}} } {{\text{G $ \alpha $ }}_{11}^{{ - \mathord{\left/ {\vphantom { - - }} \right. \kern-\nulldelimiterspace} - }} }}} \right. \kern-\nulldelimiterspace} {{\text{G $ \alpha $ }}_{11}^{{ - \mathord{\left/ {\vphantom { - - }} \right. \kern-\nulldelimiterspace} - }} }}\). The use of specific antibodies and of pharmacological agents with preferred affinity points to the contribution of m1AChR and m3AChR. In conclusion, we present two novel aspects of the physiology of the thalamocortical system by demonstrating that the depolarization of TC neurons, which is induced by the action of transmitters of ascending brainstem fibers, is governed roughly equally by both m1AChR and m3AChR and is transduced by Gαq but not by Gα11.

Keywords

Thalamic function Gene knock out TASK channels Thalamocortical relay neurons G-proteins Muscarinic ACh receptors 

Notes

Acknowledgements

This work was supported by DFG (BU 1019/7-1; PA 336/17-1), Innovative Medical Research Fund (IMF) of the University of Muenster Medical School, and IZKF Bud3/005/07. T. Broicher was a fellow of the Boehringer Ingelheim Foundation. Thanks are due to A. Jahn, E. Nass, A. Markovic, and R. Ziegler for excellent technical assistance.

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Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Tilman Broicher
    • 1
  • Nina Wettschureck
    • 2
  • Thomas Munsch
    • 3
  • Philippe Coulon
    • 1
  • Sven G. Meuth
    • 4
  • Tatyana Kanyshkova
    • 1
  • Thomas Seidenbecher
    • 1
  • Stefan Offermanns
    • 2
  • Hans-Christian Pape
    • 1
  • Thomas Budde
    • 1
    Email author
  1. 1.Institut für Physiologie IWestfälische Wilhelms-Universität MünsterMünsterGermany
  2. 2.Institut für PharmakologieUniversität HeidelbergHeidelbergGermany
  3. 3.Institut für PhysiologieOtto-von-Guericke-UniversitätMagdeburgGermany
  4. 4.Neurologische KlinikBayerische Julius-Maximilians-UniversitätWürzburgGermany

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