PubMed 21272594

Referenced in Channelpedia wiki pages of: none

Automatically associated channels: SK2 , SK3 , TRP , TRPV , TRPV1

Title: Enhancement of apamin-sensitive medium afterhyperpolarization current by anandamide and its role in excitability control in cultured hippocampal neurons.

Authors: Wei Wang, Kun Zhang, Sen Yan, Ai Li, Xinwu Hu, Liangpin Zhang, Changjin Liu

Journal, date & volume: Neuropharmacology, 2011 May , 60, 901-9

PubMed link:

Although endocannabinoid anandamide (AEA) plays an important role in synaptic signaling and neuronal survival, the underlying mechanism is not fully understood. Afterhyperpolarization (AHP) is the critical modulator of cell excitability and in turn shapes the neuronal output. Here, we examined the effects of AEA on AHP current and action potential firing in cultured rat hippocampal neurons. In whole-cell patch-clamp recording, AEA applied in the extracellular medium at nanomolar concentration enhanced medium AHP (mAHP) current and spike-frequency adaptation. Activation of apamin-sensitive, small conductance Ca(2+)-activated K(+) (SK) channels, probably SK2 and SK3 as the immunofluorescence analysis indicated, attributed largely to the AEA action on mAHP. Interestingly, AEA-induced potentiation of mAHP current was abolished by inositol 1,4,5-trisphosphate receptors (IP(3)Rs) blockade. However, the potentiation was not affected by inhibiting Ca(2+) influx or Ca(2+) release from internal store through ryanodine receptors. In addition, blockade of CB1, TRPV1 or Gi/o-protein did not attenuate the potentiation. Thus, AEA might enhance the SK mAHP currents mainly in a non-CB1/TRPV1 receptor way. Our study provides the first evidence that a functional cascade might lie among AEA, IP(3)Rs and SK channels, which may keep the membrane excitability stable in a negative-feedback manner.