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Calmodulin systems in neuronal excitability: A molecular approach to epilepsy
Author(s) -
John DeLorenzo Robert
Publication year - 1984
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.410160716
Subject(s) - calmodulin , synaptic vesicle , microbiology and biotechnology , neuroscience , chemistry , biology , postsynaptic potential , biophysics , biochemistry , vesicle , receptor , membrane , enzyme
Calmodulin is a major Ca 2+ ‐binding protein that may mediate many Ca 2+ ‐regulated processes in neuronal function. Calmodulin is present in the presynaptic nerve terminal in association with synaptic vesicles and in postsynaptic density fractions. Several calmodulin‐regulated synaptic biochemical processes have been identified. These results indicate that calmodulin may modulate some aspects of neuronal excitability. Phenytoin, carbamazepine, and the benzodiazepines inhibit Ca 2+ ‐calmodulin–regulated protein phosphorylation and neurotransmitter release by synaptic vesicles. A saturable, stereospecific membrane binding site has been identified for the benzodiazepines. The potency of the benzodiazepines to bind to these sites correlates with their ability to inhibit maximal electroshock‐induced seizures. Phenytoin and carbamazepine can displace benzodiazepine binding from these binding sites. Binding to these “anticonvulsant” sites regulates Ca 2+ ‐calmodulin–stimulated membrane protein phosphorylation and depolarization‐dependent Ca 2+ ‐calmodulin systems at the synapse. Kindling alters Ca 2+ ‐calmodulin protein phosphorylation in brain membrane. In addition, alterations in Ca 2+ ‐calmodulin kinase systems have been associated with some strains of seizuresusceptible mice. Thus, evidence from multiple sources suggests that calmodulin‐mediated processes may play a role in the development of altered neuronal excitability and in some forms of seizure disorders.