Agmatine blocked voltage-gated calcium channel in cultured rat hippocampal neurons.
OBJECTIVE
To investigate the mechanism of agmatine by observing the effect of agmatine on the voltage-gated channels in rat hippocampal neurons.


METHODS
The whole-cell patch recording technique was performed to record the voltage-gated potassium, sodium, and calcium currents in cultured rat hippocampus. Agmatine was applied directly to the single neuron using a pressure injector with microtubules.


RESULTS
Agmatine (500 micromol/L) had no significant effect on the voltage-gated potassium and sodium channels. Agmatine reversibly blocked the voltage-gated calcium channel and the blockade was enhanced with the increasing concentration of agmatine. The inhibitory rates were 21%+/-4%, 35%+/-6%, 49%+/-6%, 67%+/-4%, 69%+/-6%, 86%+/-8%, and 87%+/- 9%, at the concentration of 0.1, 0.5, 1.0, 5.0, 10.0, 50.0, and 100 micromol/L, respectively. IC50 was (1.2+/-0.4) micromol/L. Two-way ANOVA revealed that change of membrane potential displayed a significant interaction with the blockade by agmatine.


CONCLUSIONS
Agmatine reversibly blocked the voltage-gated calcium channel in rat hippocampal neurons in a concentration- and voltage-dependent way. Agmatine might perform its physiological and pharmacological effects partially by blocking the calcium channel.
Weng
Xie-Chuan
XC
Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China.
Gai
Xiao-Dan
XD
Zheng
Jian-Quan
JQ
Li
Jin
J
D000376:Agmatine / Q000494:pharmacology*; D000818:Animals; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005260:Female; D005333:Fetus; D006624:Hippocampus / Q000166:cytology*; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar
D015220:Calcium Channels; D000376:Agmatine