Resident Calmodulin Primes NMDA Receptors for Ca2+-Dependent Inactivation.
Biophys J
; 113(10): 2236-2248, 2017 Nov 21.
Article
em En
| MEDLINE
| ID: mdl-28712640
ABSTRACT
N-methyl-d-aspartate (NMDA) receptors are glutamate- and glycine-gated channels that flux Na+ and Ca2+ into postsynaptic neurons during synaptic transmission. The resulting intracellular Ca2+ transient is essential to physiological and pathological processes related to synaptic development, plasticity, and apoptosis. It also engages calmodulin (CaM) to reduce subsequent NMDA receptor activity in a process known as Ca2+-dependent inactivation (CDI). Here, we used whole-cell electrophysiology to measure CDI and computational modeling to dissect the sequence of events that underlies it. With these approaches, we estimate that CaM senses NMDA receptor Ca2+ influx at â¼9 nm from the channel pore. Further, when we controlled the frequency of Ca2+ influx through individual channels, we found that a kinetic model where apoCaM associates with channels before their activation best predicts the measured CDI. These results provide, to our knowledge, novel functional evidence for CaM preassociation to NMDA receptors in living cells. This particular mechanism for autoinhibitory feedback reveals strategies and challenges for Ca2+ regulation in neurons during physiological synaptic activity and disease.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Calmodulina
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Cálcio
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Receptores de N-Metil-D-Aspartato
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article