Elsevier

Neuropharmacology

Volume 33, Issue 1, January 1994, Pages 27-34
Neuropharmacology

Time-dependent changes in central nicotinic acetylcholine channel kinetics in excised patches

https://doi.org/10.1016/0028-3908(94)90093-0Get rights and content

Abstract

The behavior of nicotinic acetylcholine receptor (nAChR) channels in acutely isolated habenula neurons was examined by rapidly applying nicotinic agonists to outside-out membrane patches. At negative membrane potentials, applications of 100 μM nicotine routinely produced macroscopic currents due to the opening of a large number of channels. During the continuous application of the agonist, the number of open nAChR channels decreased exponentially, i.e. receptor desensitization. A progressive loss in the number of channels contributing to the peak current was observed with time following outside-out patch excision, i.e. receptor rundown. In addition to rundown there was a time-dependent increase in the rate of desensitization and a concomitant slowing in the rate of recovery from desensitization. The extent of rundown and the changes in desensitization were coupled to the time after patch excision and were not dependent on ligand activation of nicotinic channels.

References (43)

  • N.J. Woolf et al.

    Cholinergic systems in the rat brain II. Projections to the interpeduncular nucleus

    Brain Res. Bull.

    (1985)
  • P.R. Adams

    Transmitter action at endplate membrane

  • N.D. Boyd

    Two distinct kinetic phases of desensitization of acetylcholine receptors of clonal rat PC12 cells

    J. Physiol.

    (1987)
  • J.E. Chad et al.

    An enzymatic mechanism for calcium current inactivation in dialysed helix neurones

    J. Physiol.

    (1986)
  • Q.X. Chen et al.

    GABAA receptor function is regulated by phosphorylation in acutely dissociated guinea-pig neurones

    J. Physiol.

    (1990)
  • M. Covarrubias et al.

    Excision of membrane patches reduces the mean open time of nicotinic acetylcholine receptors

    Pflugers Arch.

    (1990)
  • J.P. Dilger et al.

    Desensitization of acetylcholine receptors in BC3H-1 cells

    Pflugers Arch.

    (1992)
  • F.A. Edwards et al.

    ATP receptor-mediated synaptic currents in the central nervous system

    Nature

    (1993)
  • A. Feltz et al.

    Desensitization at the frog neuromuscular junction: a biphasic process

    J. Physiol.

    (1982)
  • M.P. Frosch et al.

    Desensitization of GABA-activated currents in cultured cortical neurons

    J. Neurosci.

    (1992)
  • T. Heidmann et al.

    Rapid kinetics of agonist binding and permeability response analyzed in parallel on acetylcholine receptor rich membranes from Torpedo marmota

    Biochemistry

    (1983)
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