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Increasing small conductance Ca2+-activated potassium channel activity reverses ischemia-induced impairment of long-term potentiation.
Orfila, J E; Shimizu, K; Garske, A K; Deng, G; Maylie, J; Traystman, R J; Quillinan, N; Adelman, J P; Herson, P S.
Afiliação
  • Orfila JE; Department of Anesthesiology, University of Colorado School of Medicine, Aurora, CO, USA.
Eur J Neurosci ; 40(8): 3179-88, 2014 Oct.
Article em En | MEDLINE | ID: mdl-25080203
Global cerebral ischemia following cardiac arrest and cardiopulmonary resuscitation (CA/CPR) causes injury to hippocampal CA1 pyramidal neurons and impairs cognition. Small conductance Ca(2+)-activated potassium channels type 2 (SK2), expressed in CA1 pyramidal neurons, have been implicated as potential protective targets. Here we showed that, in mice, hippocampal long-term potentiation (LTP) was impaired as early as 3 h after recovery from CA/CPR and LTP remained impaired for at least 30 days. Treatment with the SK2 channel agonist 1-Ethyl-2-benzimidazolinone (1-EBIO) at 30 min after CA provided sustained protection from plasticity deficits, with LTP being maintained at control levels at 30 days after recovery from CA/CPR. Minimal changes in glutamate release probability were observed at delayed times after CA/CPR, implicating post-synaptic mechanisms. Real-time quantitative reverse transcriptase-polymerase chain reaction indicated that CA/CPR did not cause a loss of N-methyl-D-aspartate (NMDA) receptor mRNA at 7 or 30 days after CA/CPR. Similarly, no change in synaptic NMDA receptor protein levels was observed at 7 or 30 days after CA/CPR. Further, patch-clamp experiments demonstrated no change in functional synaptic NMDA receptors at 7 or 30 days after CA/CPR. Electrophysiology recordings showed that synaptic SK channel activity was reduced for the duration of experiments performed (up to 30 days) and that, surprisingly, treatment with 1-EBIO did not prevent the CA/CPR-induced loss of synaptic SK channel function. We concluded that CA/CPR caused alterations in post-synaptic signaling that were prevented by treatment with the SK2 agonist 1-EBIO, indicating that activators of SK2 channels may be useful therapeutic agents to prevent ischemic injury and cognitive impairments.
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Texto completo: 1 Coleções: 01-internacional Contexto em Saúde: 1_ASSA2030 Base de dados: MEDLINE Assunto principal: Isquemia Encefálica / Potenciação de Longa Duração / Canais de Potássio Ativados por Cálcio de Condutância Baixa / Hipocampo Limite: Animals Idioma: En Revista: Eur J Neurosci Ano de publicação: 2014 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Contexto em Saúde: 1_ASSA2030 Base de dados: MEDLINE Assunto principal: Isquemia Encefálica / Potenciação de Longa Duração / Canais de Potássio Ativados por Cálcio de Condutância Baixa / Hipocampo Limite: Animals Idioma: En Revista: Eur J Neurosci Ano de publicação: 2014 Tipo de documento: Article