The efficacy of physiological and pharmacological N-methyl-D-aspartate receptor block is greatly reduced under hyperbaric conditions.
Neuroscience
; 169(1): 1-7, 2010 Aug 11.
Article
en En
| MEDLINE
| ID: mdl-20457226
Human divers exposed to hyperbaric pressure may suffer from cognitive and motor impairments thought to be related to high pressure effects per ce. These effects, termed high pressure neurological syndrome (HPNS), appear at pressure above 1.1 MPa. HPNS involves CNS hyperexcitability that is partially attributed to augmented responses of the glutamatergic N-methyl-d-aspartate receptor (NMDAR). NMDAR is blocked by Mg(2+) (physiologically) and by dl-2-Amino-5-phosphonopentanoic acid (AP5, pharmacologically). We have recently reported that hyperbaric pressure augments rat hippocampus NMDAR synaptic response and generates hyperexcitability. We now test pressure effects on the blockade efficacy of Mg(2+)and AP5. Under high pressure conditions more than double [Mg(2+)](o) and [AP5](o) were needed to achieve similar effects on NMDAR synaptic response's amplitude, decay time, and time integral comparable to control conditions. [Mg(2+)](o) and [AP5](o) concentration-response curves and the concentration for 50% responses' inhibition (IC(50)s) showed similar normalized pattern at control and pressure for each parameter. We conclude that hyperbaric pressure reduces the efficacy of these NMDAR blockers that may be associated with the receptor conformational change(s). This provides additional mechanism for pressure over activation of NMDAR. Taken together with our previous reports, high pressure modification of NMDAR activity significantly contributes to CNS hyperexcitability and possibly for long term vulnerability.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Presión
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Síndrome Neurológico de Alta Presión
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2-Amino-5-fosfonovalerato
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Receptores de N-Metil-D-Aspartato
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Transmisión Sináptica
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Antagonistas de Aminoácidos Excitadores
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Magnesio
Límite:
Animals
Idioma:
En
Revista:
Neuroscience
Año:
2010
Tipo del documento:
Article
País de afiliación:
Israel
Pais de publicación:
Estados Unidos