| 10082275 |
Ren J, Ye JH, Liu PL, Krnjevic K, McArdle JJ: Cocaine decreases the glycine-induced Cl- current of acutely dissociated rat hippocampal neurons. Eur J Pharmacol. 1999 Feb 12;367(1):125-30.
The effects of cocaine on glycine-induced Cl- current (I (GLY)) of single neurons, freshly isolated from the rat hippocampal CA1 area, were studied with conventional whole-cell recording under voltage-clamp conditions. Cocaine depressed I (GLY) in a concentration-dependent manner, with an IC50 of 0.78 mM. Preincubation with 1 mM cocaine alone had no effect on I (GLY), suggesting that resting glycine channels are insensitive to cocaine. The depression of I (GLY) by cocaine was independent of membrane voltage. Internal cell dialysis with 1 mM cocaine failed to modify I (GLY). Because the depression of I (GLY) was noncompetitive, cocaine may act on the glycine receptor-chloride ionophore complex at a site distinct from that to which glycine binds. The cocaine suppression of I (GLY) was unaffected by 1 microM tetrodotoxin and 1 microM strychnine. Blockers of protein kinase C (Chelerythrine), kinase A (N-[2-((p-bromocinnamyl) amino) ethyl]-5-isoquinolinesulfonamide HCl, (H-89)) and Ca-calmodulin-dependent kinase (1-[N,O-bis (5-isoquinoline-sulfonyl)-N-methyl-L-tyrosyl]-4-phenylpiperaz ine (KN-62)) were also ineffective, which suggests that these phosphorylating mechanisms do not modulate cocaine-induced suppressant action on I (GLY). This extracellular, strychnine-independent depression of I (GLY) may contribute to cocaine-induced seizures. |
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