F.S. den Boon
- Endocannabinoids produced upon action potential firing evoke a Cl− current via type-2 cannabinoid receptors in the medial prefrontal cortex
- Plügers Archiv
- Volume | Issue number
- 466 | 12
- Pages (from-to)
- Document type
- Faculty of Science (FNWI)
- Swammerdam Institute for Life Sciences (SILS)
The functional presence of type-2 cannabinoid receptors (CB2Rs) in layer II/III pyramidal neurons of the rat medial prefrontal cortex (mPFC) was recently demonstrated. In the present study, we show that the application of the endocannabinoids (eCBs) 2-arachidonoylglycerol (2-AG) and methanandamide [a stable analog of the eCB anandamide (AEA)] can activate CB2Rs of mPFC layer II/III pyramidal neurons, which subsequently induces a Cl- current. In addition, we show that action potential (AP) firing evoked by 20-Hz current injections results in an eCB-mediated opening of Cl- channels via CB2R activation. This AP-evoked synthesis of eCBs is dependent on the Ca2+ influx through N-type voltage-gated calcium channels. Our results indicate that 2-AG is the main eCB involved in this process. Finally, we demonstrate that under physiologically relevant intracellular Cl- conditions, 20-Hz AP firing leads to a CB2R-dependent reduction in neuronal excitability. Altogether, our data indicate that eCBs released upon action potential firing can modulate, through CB2R activation, neuronal activity in the mPFC. We discuss how this may be a mechanism to prevent excessive neuronal firing.
- go to publisher's site
If you believe that digital publication of certain material infringes any of your rights or (privacy) interests, please let the Library know, stating your reasons. In case of a legitimate complaint, the Library will make the material inaccessible and/or remove it from the website. Please Ask the Library, or send a letter to: Library of the University of Amsterdam, Secretariat, Singel 425, 1012 WP Amsterdam, The Netherlands. You will be contacted as soon as possible.