 |
 Previous Article | Next Article 
The Journal of Neuroscience, October 15, 1999, 19(20):8765-8777
Cannabinoids Enhance NMDA-Elicited Ca2+ Signals in
Cerebellar Granule Neurons in Culture
Jeffrey G.
Netzeband,
Shannon M.
Conroy,
Kathy L.
Parsons, and
Donna L.
Gruol
Department of Neuropharmacology, The Scripps Research Institute, La
Jolla, California 92037
A physiological role for cannabinoids in the CNS is indicated by
the presence of endogenous cannabinoids and cannabinoid receptors. However, the cellular mechanisms of cannabinoid actions in the CNS have
yet to be fully defined. In the current study, we identified a novel
action of cannabinoids to enhance intracellular Ca2+
responses in CNS neurons. Acute application of the cannabinoid receptor
agonists R(+)-methanandamide, R(+)-WIN,
and HU-210 (1-50 nM) dose-dependently enhanced the peak
amplitude of the Ca2+ response elicited by
stimulation of the NMDA subtype of glutamate receptors (NMDARs)
in cerebellar granule neurons. The cannabinoid effect was blocked by
the cannabinoid receptor antagonist SR141716A and the
Gi/Go protein inhibitor pertussis toxin
but was not mimicked by the inactive cannabinoid analog
S( )-WIN, indicating the involvement of cannabinoid
receptors. In current-clamp studies neither R(+)-WIN nor
R(+)-methanandamide altered the membrane response to
NMDA or passive membrane properties of granule neurons, suggesting that
NMDARs are not the primary sites of cannabinoid action. Additional Ca2+ imaging studies showed that cannabinoid
enhancement of the Ca2+ signal to NMDA did not
involve N-, P-, or L-type Ca2+ channels but was
dependent on Ca2+ release from intracellular stores.
Moreover, the phospholipase C inhibitor U-73122 and the inositol
1,4,5-trisphosphate (IP3) receptor antagonist
xestospongin C blocked the cannabinoid effect, suggesting that the
cannabinoid enhancement of NMDA-evoked Ca2+ signals
results from enhanced release from IP3-sensitive
Ca2+ stores. These data suggest that the CNS
cannabinoid system could serve a critical modulatory role in CNS
neurons through the regulation of intracellular Ca2+ signaling.
Key words:
cannabinoid; methanandamide; WIN; HU-210; cerebellum; granule neuron; NMDA; intracellular calcium
Copyright © 1999 Society for Neuroscience 0270-6474/99/19208765-13$05.00/0
This article has been cited by other articles:
|
|
|
|
 
J. Ramadoss, E. R. Lunde, N. Ouyang, W.-J. A. Chen, and T. A. Cudd
Acid-sensitive channel inhibition prevents fetal alcohol spectrum disorders cerebellar Purkinje cell loss
Am J Physiol Regulatory Integrative Comp Physiol,
August 1, 2008;
295(2):
R596 - R603.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Fisyunov, V. Tsintsadze, R. Min, N. Burnashev, and N. Lozovaya
Cannabinoids Modulate the P-Type High-Voltage-Activated Calcium Currents in Purkinje Neurons
J Neurophysiol,
September 1, 2006;
96(3):
1267 - 1277.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. E. Lauckner, B. Hille, and K. Mackie
The cannabinoid agonist WIN55,212-2 increases intracellular calcium via CB1 receptor coupling to Gq/11 G proteins
PNAS,
December 27, 2005;
102(52):
19144 - 19149.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Antonelli, M. C. Tomasini, M. Tattoli, T. Cassano, S. Tanganelli, S. Finetti, E. Mazzoni, L. Trabace, L. Steardo, V. Cuomo, et al.
Prenatal Exposure to the CB1 Receptor Agonist WIN 55,212-2 Causes Learning Disruption Associated with Impaired Cortical NMDA Receptor Function and Emotional Reactivity Changes in Rat Offspring
Cereb Cortex,
December 1, 2005;
15(12):
2013 - 2020.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. L. Limke, J. J. Bearss, and W. D. Atchison
Acute Exposure to Methylmercury Causes Ca2+ Dysregulation and Neuronal Death in Rat Cerebellar Granule Cells through an M3 Muscarinic Receptor-Linked Pathway
Toxicol. Sci.,
July 1, 2004;
80(1):
60 - 68.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C.-Y. Li, T.-Y. Chin, and S.-H. Chueh
Rat cerebellar granule cells are protected from glutamate-induced excitotoxicity by S-nitrosoglutathione but not glutathione
Am J Physiol Cell Physiol,
April 1, 2004;
286(4):
C893 - C904.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Gafni, P. W. Wong, and I. N. Pessah
Non-coplanar 2,2',3,5',6-Pentachlorobiphenyl (PCB 95) Amplifies Ionotropic Glutamate Receptor Signaling in Embryonic Cerebellar Granule Neurons by a Mechanism Involving Ryanodine Receptors
Toxicol. Sci.,
January 1, 2004;
77(1):
72 - 82.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. C. Howlett, F. Barth, T. I. Bonner, G. Cabral, P. Casellas, W. A. Devane, C. C. Felder, M. Herkenham, K. Mackie, B. R. Martin, et al.
International Union of Pharmacology. XXVII. Classification of Cannabinoid Receptors
Pharmacol. Rev.,
June 1, 2002;
54(2):
161 - 202.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Ferraro, M. C. Tomasini, G. L. Gessa, B. W. Bebe, S. Tanganelli, and T. Antonelli
The Cannabinoid Receptor Agonist WIN 55,212-2 Regulates Glutamate Transmission in Rat Cerebral Cortex: an In Vivo and In Vitro Study
Cereb Cortex,
August 1, 2001;
11(8):
728 - 733.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. M. Sullivan
Cellular and Molecular Mechanisms Underlying Learning and Memory Impairments Produced by Cannabinoids
Learn. Mem.,
May 1, 2000;
7(3):
132 - 139.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
P. Schweitzer
Cannabinoids Decrease the K+ M-Current in Hippocampal CA1 Neurons
J. Neurosci.,
January 1, 2000;
20(1):
51 - 58.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
