 |
||||
|
||||
|
||||
|
||||
|
||||
The Journal of Neuroscience, May 9, 2007, 27(19):5179-5189; doi:10.1523/JNEUROSCI.5499-06.2007
Previous Article | Next Article
Development/Plasticity/Repair
TRPC3 Channels Are Necessary for Brain-Derived Neurotrophic Factor to Activate a Nonselective Cationic Current and to Induce Dendritic Spine Formation
Michelle D. Amaral andLucas Pozzo-Miller Department of Neurobiology, Civitan International Research Center and McKnight Brain Institute, University of Alabama at Birmingham, Birmingham, Alabama 35294
Correspondence should be addressed to Dr. Lucas Pozzo-Miller, Department of Neurobiology, SHEL-1002, University of Alabama at Birmingham, 1825 University Boulevard, Birmingham, AL 35294-2182. Email: lucaspm{at}uab.edu
Brain-derived neurotrophic factor (BDNF) exerts prominent effects on hippocampal neurons, but the mechanisms that initiate its actions are poorly understood. We report here that BDNF evokes a slowly developing and sustained nonselective cationic current (IBDNF) in CA1 pyramidal neurons. These responses require phospholipase C, IP3 receptors, Ca2+ stores, and Ca2+ influx, suggesting the involvement of transient receptor potential canonical subfamily (TRPC) channels. Indeed, IBDNF is absent after small interfering RNA-mediated TRPC3 knockdown. The sustained kinetics of IBDNF appears to depend on phosphatidylinositol 3-kinase-mediated TRPC3 membrane insertion, as shown by surface biotinylation assays. Slowly emerging membrane currents after theta burst stimulation are sensitive to the scavenger TrkB–IgG and TRPC inhibitors, suggesting IBDNF activation by evoked released of endogenous, native BDNF. Last, TRPC3 channels are necessary for BDNF to increase dendritic spine density. Thus, TRPC channels emerge as novel mediators of BDNF-mediated dendritic remodeling through the activation of a slowly developing and sustained membrane depolarization.
Key words: CA1 pyramidal neuron; hippocampus; TrkB receptor; biolistic transfection; surface biotinylation; confocal microscopy; organotypic slice culture; siRNA-mediated knockdown; theta-burst stimulation
Received Aug. 2, 2006; revised Feb. 14, 2007; accepted Feb. 21, 2007.
Correspondence should be addressed to Dr. Lucas Pozzo-Miller, Department of Neurobiology, SHEL-1002, University of Alabama at Birmingham, 1825 University Boulevard, Birmingham, AL 35294-2182. Email: lucaspm{at}uab.edu
This article has been cited by other articles:
J. Abramowitz and L. Birnbaumer
Physiology and pathophysiology of canonical transient receptor potential channels
FASEB J, February 1, 2009; 23(2): 297 - 328.
[Abstract] [Full Text] [PDF]
Y. Tai, S. Feng, R. Ge, W. Du, X. Zhang, Z. He, and Y. Wang
TRPC6 channels promote dendritic growth via the CaMKIV-CREB pathway
J. Cell Sci., July 15, 2008; 121(14): 2301 - 2307.
[Abstract] [Full Text] [PDF]
Y. H. Zhang, X. X. Chi, and G. D. Nicol
Brain-derived neurotrophic factor enhances the excitability of rat sensory neurons through activation of the p75 neurotrophin receptor and the sphingomyelin pathway
J. Physiol., July 1, 2008; 586(13): 3113 - 3127.
[Abstract] [Full Text] [PDF]
F.-W. Zhou, S. G. Matta, and F.-M. Zhou
Constitutively Active TRPC3 Channels Regulate Basal Ganglia Output Neurons
J. Neurosci., January 9, 2008; 28(2): 473 - 482.
[Abstract] [Full Text] [PDF]
M. D. Amaral and L. Pozzo-Miller
BDNF Induces Calcium Elevations Associated With IBDNF, a Nonselective Cationic Current Mediated by TRPC Channels
J Neurophysiol, October 1, 2007; 98(4): 2476 - 2482.
[Abstract] [Full Text] [PDF]
|
|
|
|
 |
|