Role for calcium/calmodulin-dependent protein kinase II in the p75-mediated regulation of sympathetic cholinergic transmission.
Proc Natl Acad Sci U S A
; 103(8): 2915-9, 2006 Feb 21.
Article
em En
| MEDLINE
| ID: mdl-16476997
ABSTRACT
Neurotrophins regulate sympathetic neuron cotransmission by modulating the activity-dependent release of norepinephrine and acetylcholine. Nerve growth factor promotes excitatory noradrenergic transmission, whereas brain-derived neurotrophic factor (BDNF), acting through the p75 receptor, increases inhibitory cholinergic transmission. This regulation of corelease by target-derived factors leads to the functional modulation of myocyte beat rate in neuron-myocyte cocultures. Calcium/calmodulin-dependent protein kinase II (CaMKII) has been implicated in the control of both pre- and postsynaptic mechanisms of synaptic plasticity. We demonstrate that CaMKII acts in conjunction with p75 signaling to regulate cholinergic transmission between sympathetic neurons and heart cells. Inhibition of presynaptic CaMKII prevents the BDNF-dependent shift to inhibitory neurotransmission, whereas presynaptic expression of a constitutively active CaMKII results in inhibitory neurotransmission in the absence of added BDNF, suggesting that activation of presynaptic CaMKII is both necessary and sufficient for a shift from excitatory to inhibitory transmission. Several isozymes of CaMKII are expressed in sympathetic neurons, with the delta-CaMKII being activated by BDNF and nerve growth factor. Activated CaMKII is less effective at promoting cholinergic transmission in the absence of p75 signaling, demonstrating that p75 and CaMKII act to coordinate neurotransmitter selection in sympathetic neurons.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Sistema Nervoso Simpático
/
Proteínas Quinases Dependentes de Cálcio-Calmodulina
/
Transmissão Sináptica
/
Receptor de Fator de Crescimento Neural
Limite:
Animals
Idioma:
En
Revista:
Proc Natl Acad Sci U S A
Ano de publicação:
2006
Tipo de documento:
Article
País de afiliação:
Estados Unidos