Veratridine-induced intoxication: an in vitro model for the characterization of anti-ischemic compounds?
Due to the complexity of ischemia-induced cellular dysfunction many different pharmacological approaches have been tested to improve cellular ischemia resistance. However, despite the importance of [Na+]i for ischemia-induced dysfunction, only very few studies have investigated the contribution of the Na+ channel to ischemia-induced failure of intracellular ion homeostasis. Since an activation of Na+ channels by veratridine also results in a failure of intracellular ion homeostasis, the veratridine- and ischemia-induced alterations of cellular function were compared. Moreover, despite the difference in the electrophysiological changes induced by veratridine and ischemia, the possible involvement of a slowly inactivating, less selective Na+ channel in both veratridine- and ischemia-induced cellular dysfunction is discussed. As a conclusion it is suggested that veratridine intoxication could be a helpful in vitro method for the characterization of putative anti-ischemic compounds.
Wermelskirchen
D
D
Janssen Research Foundation, Neuss, Germany.
Wilffert
B
B
Peters
T
T
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D006801:Humans; D007473:Ion Channels / Q000187:drug effects; D007511:Ischemia / Q000188:drug therapy*; D014701:Veratridine / Q000633:toxicity*
D007473:Ion Channels; D014701:Veratridine