Luzindole,a melatonin receptor antagonist,inhibits the transient outward K+ current in rat cerebellar granule cells |
| |
Authors: | Zhou Mi-ou Jiao Song Liu Zheng Zhang Zhi-hong Mei Yan-ai |
| |
Institution: | Center for Brain Science Research, Department of Physiology and Biophysics, School of Life Sciences, Fudan University, Shanghai 200433, China |
| |
Abstract: | The inhibitory effect of the melatonin receptor antagonist luzindole on voltage-activated transient outward K+ current (IK(A)) was investigated in cultured rat cerebellar granule cells using the whole cell voltage-clamp technique. At the concentration of 1 μM to 1 mM, luzindole reversibly inhibited IK(A) in a concentration-dependent manner. In addition to reducing the current amplitude of IK(A),luzindole accelerated the fast inactivation of IK(A) channels and shifted the curves of voltage-dependent steady-state activation and inactivation of IK(A) by +6.6 mV and −7.0 mV, respectively. The inhibitory effect of luzindole was neither use-dependent nor voltage-dependent, suggesting that the binding affinity of luzindole to IK(A) channels is state-dependent. Including luzindole in the pipette solution, or extracellular application of 4 P-PDOT, an antagonist of melatonin receptors, did not change the luzindole-induced inhibitory effect on the IK(A) current, indicating that luzindole exerts its channel blocking inhibitory action at the extracellular mouth of the channel, and that the effect is not due to action of the melatonin receptors. Our data are the first demonstration that luzindole is able to block transient outward K+ channels in rat cerebellar granule cells in a state-dependent manner, likely associated with extracellular interaction of the drug with the IK(A) inactivation gate. |
| |
Keywords: | Luzindole K+ current Cerebellar granule cell |
本文献已被 ScienceDirect PubMed 等数据库收录! |
|