Presynaptic K+ channel modulation is a crucial ionic basis of neuronal damage induced by ischemia in rat hippocampal CA1 pyramidal neurons.
The ischemia-induced synaptic potentiation (ISP) during and/or after brain ischemia has been suggested to be one of the crucial factors responsible for irreversible neuronal damage of hippocampal CA1 pyramidal neurons. However, the presynaptic modulation mechanism that leads to neuronal damage during and/or after ischemia was still unknown. By combining electrophysiological methods and infra-red differential interference contrast (IR-DIC) imaging procedures, we showed for the first time that ISP is the result of extraordinary presynaptic depolarization in association with the suppression of 4-aminopyridine (4-AP) sensitive K(+) channels at the presynaptic sites. Furthermore, we also showed that the 4-AP sensitive presynaptic K(+) channels played a crucial role in inducing neuronal damage at a very acute phase of ischemia-induced neuronal damage and would be a therapeutic target against the neuronal damage after brain ischemia.
Takagi
Hiroshi
H
Second Department of Physiology, Shinshu University School of Medicine, Matsumoto, Nagano, Japan.
Kodama
Kunihiko
K
Saito
Minoru
M
Suzuki
Hideo
H
D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism*; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology*; D011188:Potassium / Q000378:metabolism*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000378:metabolism*; D017966:Pyramidal Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar
D026902:Potassium Channel Blockers; D015221:Potassium Channels; D015761:4-Aminopyridine; D011188:Potassium