Mechanisms underlying low [Ca(2+)](o)-induced increased excitability of hippocampal neurons.
OBJECTIVE
Concentration of extracellular calcium ([Ca(2+)](o)) in the central nervous system decreases substantially in different conditions. It results in facilitating neuronal excitability. The goal of this study is to examine the mechanisms of enhanced neuronal excitation in low [Ca(2+)](o) in order to provide new clues to treat the hyperexcitability diseases in clinic.


METHODS
Whole-cell patch-clamp technique and neuron culture were used in the study.


RESULTS
The firing threshold of cultured hippocampal neurons decreased markedly in low [Ca(2+)](o) saline. Unexpectedly, apamine and isoprenaline, antagonists of medium afterhyperpolarization (mAHP) and slow AHP (sAHP) respectively, had no statistic significant effect on excitability of neurons. TTX at a low concentration was sufficient to inhibit I(NaP), which blocked the increase of firing frequency in low [Ca(2+)](o). It also reduced the number of spikes in normal [Ca(2+)](o).


CONCLUSIONS
These results suggest that in cultured hippocampal neurons, modulation of spiking threshold but not AHP may cause the increased excitability in low [Ca(2+)](o).
Yue
Wei-Dong
WD
Department of Neurology, the Second Affiliated Hospital of Harbin Medical University, Harbin, China.
Zhang
Yun-Hong
YH
Gu
Feng
F
Wang
Jing
J
Zhang
Ji-Ye
JY
Gu
Rui-Min
RM
D000200:Action Potentials / Q000187:drug effects*; D000818:Animals; D001030:Apamin / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D004622:Embryo, Mammalian; D006624:Hippocampus / Q000166:cytology*; D009474:Neurons / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D051381:Rats; D026941:Sodium Channel Blockers / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology
D026941:Sodium Channel Blockers; D001030:Apamin; D013779:Tetrodotoxin; D002118:Calcium