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Cannabinoids decrease the K(+) M-current in hippocampal CA1 neurons.

P Schweitzer1

  • 1Department of Neuropharmacology, The Scripps Research Institute, La Jolla, California 92037, USA. pschweitzer@scripps.edu

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
|January 11, 2000
PubMed
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Cannabinoids decrease the M-current (I(M)) in rat hippocampal neurons, increasing neuronal excitability. This effect is mediated by cannabinoid receptor 1 (CB1) activation and enhances postsynaptic activity.

Area of Science:

  • Neuroscience
  • Pharmacology

Background:

  • Cannabinoid effects on neuronal excitability are not fully understood.
  • Sustained conductances play a critical role in regulating neuronal firing.

Purpose of the Study:

  • To investigate the postsynaptic effects of cannabinoid agonists on CA1 pyramidal neurons.
  • To determine the specific ion currents modulated by cannabinoids in the hippocampus.

Main Methods:

  • Intracellular voltage-clamp recordings in rat hippocampal slices.
  • Application of cannabinoid agonists (WIN55212-2, methanandamide) and antagonists (SR141716).
  • Assessment of M-current (I(M)) and h-current (I(h)) using electrophysiological techniques.

Main Results:

  • Cannabinoids elicited an inward current by decreasing the M-current (I(M)).

Related Experiment Videos

  • This effect was voltage-dependent, reversed near K(+) equilibrium potential, and blocked by SR141716.
  • Cannabinoids did not affect the h-current (I(h)).
  • Cannabinoid-induced I(M) decrease was independent of muscarinic receptor activation.

    • Conclusions:

    • Cannabinoids postsynaptically augment CA1 pyramidal neuron excitability.
    • This augmentation occurs via specific inhibition of the persistent voltage-dependent M-current (I(M)).
    • Cannabinoid and muscarinic receptor pathways independently modulate I(M).