title: Enhancement of apamin-sensitive medium afterhyperpolarization current by anandamide and its role in excitability control in cultured hippocampal neurons.
abstract: 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.
authors.affiliation: Department of Physiology, Tongji Medical College, Huazhong University of Science and Technology, No. 13, Hangkong Road, Wuhan, Hubei Province 430030, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Kun
authors.initials: K
authors.lastname: Zhang
authors.forename: Sen
authors.initials: S
authors.lastname: Yan
authors.forename: Ai
authors.initials: A
authors.lastname: Li
authors.forename: Xinwu
authors.initials: X
authors.lastname: Hu
authors.forename: Liangpin
authors.initials: L
authors.lastname: Zhang
authors.forename: Changjin
authors.initials: C
authors.lastname: Liu
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn; D001030:Apamin / Q000494:pharmacology*; D001095:Arachidonic Acids / Q000494:pharmacology / Q000502:physiology*; D002118:Calcium / Q000378:metabolism / Q000502:physiology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D018929:Cell Culture Techniques; D063388:Endocannabinoids; D019204:GTP-Binding Proteins / Q000037:antagonists & inhibitors; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology*; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000037:antagonists & inhibitors / Q000502:physiology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009433:Neural Inhibition / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D018408:Patch-Clamp Techniques; D053284:Polyunsaturated Alkamides / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors / Q000502:physiology; D019837:Ryanodine Receptor Calcium Release Channel; D051640:Small-Conductance Calcium-Activated Potassium Channels / Q000819:agonists / Q000378:metabolism; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors
chemical_list: D001095:Arachidonic Acids; D002121:Calcium Channel Blockers; D063388:Endocannabinoids; D053496:Inositol 1,4,5-Trisphosphate Receptors; D053284:Polyunsaturated Alkamides; D043884:Receptor, Cannabinoid, CB1; D019837:Ryanodine Receptor Calcium Release Channel; D051640:Small-Conductance Calcium-Activated Potassium Channels; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; D001030:Apamin; D019204:GTP-Binding Proteins; D002118:Calcium; C078814:anandamide