The effect of cocaine on K+ currents activated by the K ATP channel opener cromakalim was investigated in follicular cells of Xenopus oocytes. The results indicate that cocaine in the concentration range of 3-500 μM reversibly inhibits cromakalim-induced K+ currents. The IC50 value for cocaine was 96 μM. Inhibition of the cromakalim-activated K+ current by cocaine was noncompetitive and voltage independent. Pretreatment with the Ca2+ chelator BAPTA did not modify the cocaine-induced inhibition of cromakalim-induced K+ currents, suggesting that Ca2+-activated second messenger pathways are not involved in the actions of cocaine. Outward K+ currents activated by the application of 8-Br-cAMP or forskolin were also inhibited by cocaine. The EC50 and slope values for the activation of K + currents by cromakalim were 184±19 μM and 1.14 in the absence of cocaine as compared to 191±23 μM and 1.03 in the presence of cocaine (300 μM). Cocaine also blocked K+ currents mediated through C-terminally deleted form of Kir6.2 (KirΔC26) in the absence of sulfonylurea receptor with an IC50 value of 87 μM, suggesting that cocaine interacts directly with the channel forming Kir6.2 subunit. Radioligand binding studies indicated that cocaine (100 μM) did not affect the binding characteristics of the KATP ligand, [3H] glibenclamide. These results demonstrate that cromakalim-activated K + currents in follicular cells of Xenopus oocytes are modulated by cocaine.
|Number of pages||8|
|Journal||Naunyn-Schmiedeberg's Archives of Pharmacology|
|Publication status||Published - Feb 2004|
- K channels
- Xenopus oocyte
ASJC Scopus subject areas