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.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
SK may itself be a molecular target of AEA.
“SK may itself be a molecular target of AEA (Wang et al., 2011).”
From The endocannabinoid system as a target for novel anxiolytic drugs (2017) · cites this paper as Wang et al., 2011
Cites
Isolation and Structure of a Brain Constituent That Binds to the Cannabinoid Receptor
Devane, W. A., Hanuš, L., Breuer, A., Pertwee, R. G., Stevenson, L. A., Griffin, G., Gibson, D., Mandelbaum, A., Etinger, A., & Mechoulam, R. (1992) · Science · doi:10.1126/science.1470919 · Cited by 5,633 · see citing works
GPR55 is a cannabinoid receptor that increases intracellular calcium and inhibits M current
Lauckner, J. E., Jensen, J. B., Chen, H.-Y., Lu, H., Hille, B., & Mackie, K. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0711278105 · Cited by 710 · see citing works
Storm, J. F. (1987) · The Journal of Physiology · doi:10.1113/jphysiol.1987.sp016517 · Cited by 698 · see citing works
Cannabinoid physiology and pharmacology: 30 years of progress
Howlett, A. C., Breivogel, C. S., Childers, S. R., Deadwyler, S. A., Hampson, R. E., & Porrino, L. J. (2004) · Neuropharmacology · doi:10.1016/j.neuropharm.2004.07.030 · Cited by 608 · see citing works
Marrion, N. V., & Tavalin, S. J. (1998) · Nature · doi:10.1038/27674 · Cited by 546 · see citing works
Ca2+-activated K+ channels: molecular determinants and function of the SK family
Stocker, M. (2004) · Nature reviews. Neuroscience · doi:10.1038/nrn1516 · Cited by 534 · see citing works
Prostaglandins and cycloxygenases in the spinal cord
Vanegas, H., & Schaible, H. (2001) · Progress in Neurobiology · doi:10.1016/s0301-0082(00)00063-0 · Cited by 416 · see citing works
Gu, N., Vervaeke, K., Hu, H., & Storm, J. F. (2005) · The Journal of Physiology · doi:10.1113/jphysiol.2005.086835 · Cited by 363 · see citing works
Functional Conversion Between A-Type and Delayed Rectifier K + Channels by Membrane Lipids
Oliver, D., Lien, C., Soom, M., Baukrowitz, T., Jónás, P., & Fakler, B. (2004) · Science · doi:10.1126/science.1094113 · Cited by 317 · see citing works
The endocannabinoid anandamide is a direct and selective blocker of the background K+ channel TASK‐1
Maingret, F., Patel, A. J., Lazdunski, M., & Honoré, É. (2001) · The EMBO Journal · doi:10.1093/emboj/20.1.47 · Cited by 313 · see citing works
Bond, C. T. (2004) · Journal of Neuroscience · doi:10.1523/jneurosci.0182-04.2004 · Cited by 291 · see citing works
Anandamide acts as an intracellular messenger amplifying Ca2+ influx via TRPV1 channels
van der Stelt, M., Trevisani, M., Vellani, V., PETROCELLIS, L. D., Moriello, A. S., Campi, B., McNaughton, P. A., Geppetti, P., & Marzo, V. D. (2005) · The EMBO Journal · doi:10.1038/sj.emboj.7600784 · Cited by 243 · see citing works
Hammond, R. S., Bond, C. T., Strassmaier, T., Jennifer Ngo-Anh, T., Adelman, J. P., Maylie, J., & Stackman, R. W. (2006) · The Journal of Neuroscience · doi:10.1523/jneurosci.4106-05.2006 · Cited by 215 · see citing works
Waldeck‐Weiermair, M., Zoratti, C., Osibow, K., Balenga, N. A. B., Goessnitzer, E., Waldhoer, M., Malli, R., & Graier, W. F. (2008) · Journal of Cell Science · doi:10.1242/jcs.020958 · Cited by 177 · see citing works
Cannabidiol-induced intracellular Ca2+ elevations in hippocampal cells
Drysdale, A. J., Ryan, D., Pertwee, R. G., & Platt, B. (2005) · Neuropharmacology · doi:10.1016/j.neuropharm.2005.11.008 · Cited by 160 · see citing works
Pedarzani, P., McCutcheon, J. E., Rogge, G., Jensen, B., Christophersen, P., Hougaard, C. Ø., Strøbæk, D., & Stocker, M. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m509610200 · Cited by 158 · see citing works
Modulation of recombinant and native neuronal SK channels by the neuroprotective drug riluzole
Cao, Y., Dreixler, J. C., Couey, J. J., & Houamed, K. M. (2002) · European Journal of Pharmacology · doi:10.1016/s0014-2999(02)01987-8 · Cited by 122 · see citing works
Endocannabinoids and Traumatic Brain Injury
Mechoulam, R., & Shohami, E. (2007) · Molecular Neurobiology · doi:10.1007/s12035-007-8008-6 · Cited by 112 · see citing works
Protective activation of the endocannabinoid system during ischemia in dopamine neurons
Melis, M., Pillolla, G., Bisogno, T., Minassi, A., Petrosino, S., Perra, S., Muntoni, A. L., Lutz, B., Gessa, G. L., & Marsicano, G. (2006) · Neurobiology of Disease · doi:10.1016/j.nbd.2006.04.010 · Cited by 101 · see citing works
Power, J., & Sah, P. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.4310-07.2008 · Cited by 78 · see citing works
The Molecular Basis of Voltage-gated Ca 2+ Channel Diversity: Is It Time for T?
Randall, A. D. (1998) · The Journal of Membrane Biology · doi:10.1007/s002329900327 · Cited by 66 · see citing works
Brennan, A. R., Dolinsky, B., Vu, M.-A. T., Stanley, M., Yeckel, M. F., & Arnsten, A. F. T. (2008) · Learning & Memory · doi:10.1101/lm.767408 · Cited by 63 · see citing works
Chen, Q., & Toney, G. M. (2009) · The Journal of Physiology · doi:10.1113/jphysiol.2009.175364 · Cited by 46 · see citing works
Köfalvi, A., Pereira, M. F., Rebola, N., Rodrigues, R. J., Oliveira, C. R., & Cunha, R. A. (2007) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0707252 · Cited by 42 · see citing works
Activation of large-conductance, Ca2+-activated K+ channels by cannabinoids
Sade, H., Muraki, K., Ohya, S., Hatano, N., & Imaizumi, Y. (2005) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00482.2004 · Cited by 42 · see citing works
Lozovaya, N., Min, R., Tsintsadze, V., & Burnashev, N. (2009) · Cell Calcium · doi:10.1016/j.ceca.2009.07.007 · Cited by 40 · see citing works
Dreixler, J. C., Jenkins, A., Cao, Y., Roizen, J. D., & Houamed, K. M. (2000) · Anesthesia & Analgesia · doi:10.1097/00000539-200003000-00040 · Cited by 38 · see citing works
Activation of SK channels inhibits epileptiform bursting in hippocampal CA3 neurons
Lappin, S. C., Dale, T., Brown, J. T., Trezise, D. J., & Davies, C. H. (2005) · Brain Research · doi:10.1016/j.brainres.2005.10.024 · Cited by 37 · see citing works
Yanovsky, Y., Zhang, W., & Misgeld, U. (2005) · Neuroscience · doi:10.1016/j.neuroscience.2005.08.026 · Cited by 28 · see citing works
The endocannabinoid anandamide inhibits potassium conductance in rat cortical astrocytes
Vignali, M., Benfenati, V., Caprini, M., Anděrová, M., Nobile, M., & Ferroni, S. (2008) · Glia · doi:10.1002/glia.20807 · Cited by 16 · see citing works
Modulation of sensory neuron potassium conductances by anandamide indicates roles for metabolites
Evans, R. M., Wease, K. N., MacDonald, C. J., Khairy, H. A., Ross, R. A., & Scott, R. H. (2008) · British Journal of Pharmacology · doi:10.1038/bjp.2008.93 · Cited by 12 · see citing works
Sang, N., Zhang, J., & Chen, C. (2010) · Neurochemistry International · doi:10.1016/j.neuint.2010.01.001 · Cited by 12 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Endocannabinoids and Their Pharmacological Actions
Pertwee, R. G. (2015) · Handbook of experimental pharmacology · doi:10.1007/978-3-319-20825-1_1 · Cited by 302 · see citing works
The endocannabinoid system as a target for novel anxiolytic drugs
Patel, S., Hill, M. N., Cheer, J. F., Wotjak, C. T., & Holmes, A. (2017) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2016.12.033 · Cited by 233 · see citing works
Sun, Z., Han, J., Zhao, W., Zhang, Y., Wang, S., Ye, L., Liu, T., & Zheng, L. (2014) · International Journal of Molecular Sciences · doi:10.3390/ijms151018362 · Cited by 76 · see citing works
Marty, V. N., & Spigelman, I. (2012) · Frontiers in Neuroscience · doi:10.3389/fnins.2012.00086 · Cited by 57 · see citing works
Cyclooxygenase-2 inhibition reduces stress-induced affective pathology
Gamble-George, J. C., Baldi, R., Halladay, L., Kocharian, A., Hartley, N., Silva, C. G., Roberts, H., Haymer, A., Marnett, L. J., Holmes, A., et al. (2016) · eLife · doi:10.7554/elife.14137 · Cited by 55 · see citing works
KCa2 and KCa3 Channels in Learning and Memory Processes, and Neurodegeneration
Kuiper, E. F. E., Nelemans, A., Luiten, P. G. M., Nijholt, I. M., Dolga, A. M., & Eisel, U. (2012) · Frontiers in Pharmacology · doi:10.3389/fphar.2012.00107 · Cited by 39 · see citing works
Qian, W., Yin, N., Gao, F., Miao, Y., Li, Q., Li, F., Sun, X., Yang, X., & Wang, Z. (2017) · Neuropharmacology · doi:10.1016/j.neuropharm.2017.04.027 · Cited by 37 · see citing works
Liu, K., Gui, B., Sun, Y., Shi, N., Gu, Z., Zhang, T., & Sun, X. (2012) · Cell Calcium · doi:10.1016/j.ceca.2012.11.014 · Cited by 18 · see citing works
Yan, L., Pan, M., Fu, M., Wang, J., Huang, W., & Qian, H. (2016) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2016.01.009 · Cited by 12 · see citing works
Báldi, R., Ghosh, D., Grueter, B. A., & Patel, S. (2016) · Current Protocols in Neuroscience · doi:10.1002/cpns.8 · Cited by 10 · see citing works
Hegemann, R. U., & Abraham, W. C. (2021) · Journal of Neurophysiology · doi:10.1152/jn.00514.2020 · Cited by 5 · see citing works
Zhang, Y., Xie, H., Lei, G., Li, F., Pan, J., Liu, C., Liu, Z., Liu, L., & Cao, X. (2014) · Neural Regeneration Research · doi:10.4103/1673-5374.131607 · Cited by 5 · see citing works
Kcnn3 as a target for treating aberrant behaviors in stressed, ethanol-dependent micePreprint
Padula, A. E., Rinker, J. A., Khan, F., Lopez, M. F., Mulligan, M. K., Williams, R. W., Becker, H. C., & Mulholland, P. J. (2019) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/734970
The endocannabinoid-mediated control of neuronal excitability
Debanne, D., & Incontro, S. (2025) · Handbook of behavioral neuroscience · doi:10.1016/b978-0-443-13908-6.00003-7
- Authors
- Wang, W., Zhang, K., Yan, S., Li, A., Hu, X., Zhang, L., & Liu, C.
- Affiliations
- Huazhong University of Science and Technology (CN)
- Corresponding author
- Liu, Changjin
- Venue
- Neuropharmacology
- Publisher
- Elsevier BV
- Published
- 2011-05
- Volume
- 60
- Issue
- 6
- Pages
- 901-909
- ISSN
- 0028-3908 (ISSN-L)
- OpenAlex
- W2079489804
- Cited by
- 15
- References
- 32
- Citations by year
- 2025: 1 · 2021: 1 · 2019: 1 · 2017: 2 · 2016: 4 · 2015: 1 · 2014: 2 · 2012: 3
- FWCI
- 1.17
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuropharmacology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Specialized Research Fund for the Doctoral Program of Higher Education of China (20070487109)
- Topics
- Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- anandamide, small conductance calcium-activated potassium channels, SK2, SK3, IP3 receptor, hippocampal neurons, neuronal excitability, spike frequency adaptation, endocannabinoid signaling, negative feedback regulation
- MeSH terms
- Action Potentials, Animals, Animals, Newborn, Apamin, Arachidonic Acids, Calcium, Calcium Channel Blockers, Hippocampus, Membrane Potentials, Neural Inhibition, Neurons, Rats, Sprague-Dawley, Patch-Clamp Techniques, Cell Culture Techniques, GTP-Binding Proteins, Ryanodine Receptor Calcium Release Channel, Receptor, Cannabinoid, CB1, TRPV Cation Channels, Rats, Small-Conductance Calcium-Activated Potassium Channels, Polyunsaturated Alkamides, Inositol 1,4,5-Trisphosphate Receptors, Endocannabinoids
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
