Role of extracellular sialic acid in regulation of neuronal and network excitability in the rat hippocampus. J Neurosci 2007 Oct 24;27(43):11587-94
Date
10/26/2007Pubmed ID
17959801Pubmed Central ID
PMC6673228DOI
10.1523/JNEUROSCI.2033-07.2007Scopus ID
2-s2.0-35548931238 55 CitationsAbstract
The extracellular membrane surface contains a substantial amount of negatively charged sialic acid residues. Some of the sialic acids are located close to the pore of voltage-gated channel, substantially influencing their gating properties. However, the role of sialylation of the extracellular membrane in modulation of neuronal and network activity remains primarily unknown. The level of sialylation is controlled by neuraminidase (NEU), the key enzyme that cleaves sialic acids. Here we show that NEU treatment causes a large depolarizing shift of voltage-gated sodium channel activation/inactivation and action potential (AP) threshold without any change in the resting membrane potential of hippocampal CA3 pyramidal neurons. Cleavage of sialic acids by NEU also reduced sensitivity of sodium channel gating and AP threshold to extracellular calcium. At the network level, exogenous NEU exerted powerful anticonvulsive action both in vitro and in acute and chronic in vivo models of epilepsy. In contrast, a NEU blocker (N-acetyl-2,3-dehydro-2-deoxyneuraminic acid) dramatically reduced seizure threshold and aggravated hippocampal seizures. Thus, sialylation appears to be a powerful mechanism to control neuronal and network excitability. We propose that decreasing the amount of extracellular sialic acid residues can be a useful approach to reduce neuronal excitability and serve as a novel therapeutic approach in the treatment of seizures.
Author List
Isaev D, Isaeva E, Shatskih T, Zhao Q, Smits NC, Shworak NW, Khazipov R, Holmes GLAuthor
Olena Isaeva PhD Assistant Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Action PotentialsAnimals
Extracellular Fluid
Hippocampus
Membrane Potentials
N-Acetylneuraminic Acid
Nerve Net
Neurons
Rats
Rats, Sprague-Dawley
