[The effect of the environment ion composition upon the blockade of the AMPA receptor channels].
It is well known that ion composition significantly affects action of various pharmacological agents. In the present work we studied influence of external sodium on the block of Ca2+ -permeable AMPA receptor channels by dicationic derivative of phenylcyclohexyl IEM-1925. Experiments were performed on native receptors of giant striatal interneurones isolated from the rat brain slices. Registrations were done with the aid of whole-cell patch clamp technique. We found that partial substitution of external sodium by sucrose potentiated the blocking action of IEM-1925. The effect was voltage-dependent, being more pronounced at hyperpolarized voltages. The analysis of kinetics of the IEM-1925 action demonstrated that lowering of external sodium facilitated blocking action, whereas stability of the drug-channel complex remained unaffected. We conclude that the current carrying sodium ions compete with blocking cation IEM-1925 for an intrapore binding site.
Tikhonova
T B
TB
Magazanik
L G
LG
Tikhonov
D B
DB
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D003342:Corpus Striatum / Q000166:cytology / Q000378:metabolism*; D003959:Diamines / Q000494:pharmacology*; D015640:Ion Channel Gating / Q000187:drug effects; D007477:Ions / Q000378:metabolism; D018408:Patch-Clamp Techniques; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism*
D003959:Diamines; C406748:IEM 1925; D007477:Ions; D000644:Quaternary Ammonium Compounds; D018091:Receptors, AMPA; D012964:Sodium; D002118:Calcium