Referenced in: none

Automatically associated channels: Cav2.2 , SK2

Title: KCa2 channels activation prevents [Ca2+]i deregulation and reduces neuronal death following glutamate toxicity and cerebral ischemia.

Authors: A M Dolga, N Terpolilli, F Kepura, I M Nijholt, H-G Knaus, B D'Orsi, J H M Prehn, U L M Eisel, T Plant, N Plesnila, C Culmsee

Journal, date & volume: Cell Death Dis, 2011 , 2, e147

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/21509037

Abstract
Exacerbated activation of glutamate receptor-coupled calcium channels and subsequent increase in intracellular calcium ([Ca2+]i) are established hallmarks of neuronal cell death in acute and chronic neurological diseases. Here we show that pathological [Ca2+]i deregulation occurring after glutamate receptor stimulation is effectively modulated by small conductance calcium-activated potassium (KCa2) channels. We found that neuronal excitotoxicity was associated with a rapid downregulation of KCa2.2 channels within 3 h after the onset of glutamate exposure. Activation of KCa2 channels preserved KCa2 expression and significantly reduced pathological increases in [Ca2+]i providing robust neuroprotection in vitro and in vivo. These data suggest a critical role for KCa2 channels in excitotoxic neuronal cell death and propose their activation as potential therapeutic strategy for the treatment of acute and chronic neurodegenerative disorders.