TRPC6 Inhibited NMDA Current in Cultured Hippocampal Neurons
- PDF / 486,625 Bytes
- 7 Pages / 595.276 x 790.866 pts Page_size
- 76 Downloads / 178 Views
ORIGINAL PAPER
TRPC6 Inhibited NMDA Current in Cultured Hippocampal Neurons Hongmei Shen • Jie Pan • Longlu Pan Nianjiao Zhang
•
Received: 10 October 2012 / Accepted: 28 February 2013 / Published online: 15 March 2013 Ó Springer Science+Business Media New York 2013
Abstract N-methyl-D-aspartate (NMDA) receptors play a key role in excitatory synaptic transmission, plasticity and neural development, and they also mediate excitotoxicity that is involved in both acute neuronal damage and chronic neurodegenerative diseases. Regulation of the NMDA channel activity is critical for the pathological processes of these diseases. The canonical transient receptor potential channels (TRPCs) are Ca2?-permeable nonselective cation channels with various physiological functions, including promoting neuronal survival. Here, we reported that TRPC6, a member of the TRPC family, inhibited the NMDA-induced current in primary cultured hippocampal neurons. Overexpression of TRPC6 or application of 1-oleoyl-2-acetyl-sn-glycerol, a compound known to activate TRPCs, inhibited the NMDA-induced current in these neurons assayed by the whole-cell patch-clamp recording. Consistently, downregulation of TRPC6 or application of SKF96365, a compound known to inhibit TRPCs, enhanced this current. The peak amplitude of the NMDA current in the neurons isolated from TRPC6 transgenic mice was greatly suppressed than that in the neurons isolated from the wild-type littermates. Furthermore, TRPC6 might activate calcineurin to inhibit the activity of NMDA receptors in cultured hippocampal neurons. Together, these results suggested that TRPC6 might be a novel negative modulator of NMDA receptors. Keywords NMDA receptors TRPC channels Hippocampal neurons
H. Shen (&) J. Pan L. Pan N. Zhang Jiangsu Key Laboratory of Neuroregeneration and Institute of Nautical Medicine, Nantong University, 19 Qixiu Road, Nantong 226001, China e-mail: [email protected]
Introduction Glutamate is a major excitatory neurotransmitter in the mammalian central nervous system (CNS). It plays an essential role in a wide array of physiological processes, including excitatory synaptic transmission, plasticity and neural development (Greengard 2001). However, excessive accumulation of glutamate or overstimulation of its receptors induces the excitotoxicity. Excitotoxicity in the CNS is involved in acute neuronal damage, including traumatic brain injury and stroke, or in chronic neurodegenerative diseases, such as Huntington’s chorea, Alzheimer’s disease and parkinsonism (Blandini et al. 1996). Glutamate can activate three classes of ionotropic postsynaptic receptors, namely AMPA, N-methyl-D-aspartate (NMDA) and kainate receptors. NMDA receptors play a key role in mediating excitotoxicity due to their high permeability to Ca2? (Burnashev et al. 1995; Garaschuk et al. 1996; Mayer and Westbrook 1987; Rogers and Dani 1995; Schneggenburger et al. 1993). The NMDA receptors are heteromeric complexes formed by three kinds of subunits, GluN1, GluN2 and GluN3. The GluN1 subunits are e
Data Loading...
