The effect of single cerebroside compounds on activation of BKCa channels
- 医学院－已发表论文 
We have previously shown that a mixture of cerebrosides obtained from dried tubers of herb Typhonium giganteum Engl. plays a neuroprotective role in the ischemic brain through its effect on activation of BKCa channels. It is very curious to know whether a single pure cerebroside compound could activate the BKCa channel as well. This study explored the possible effects of pure cerebroside compounds, termitomycesphins A and B, on the BKCa channel activation. Both termitomycesphins A and B activated the BKCa channels at micromole concentration without significant difference. Termitomycesphin A increased the single channel open probability of the BKCa channels in a dose-dependent manner without modifying the single channel conductance. Termitomycesphin A activated BKCa channel more efficiently when it was applied to the cytoplasmic face of the membrane, suggesting that binding site for termitomycesphin A is located at the cytoplasmic side. Termitomycesphin A shifted the voltage-dependent activation curve to less positive membrane potentials and the Ca2+-dependent activation curve of the channel upwards, suggesting that termitomycesphin A could activate the channels even without intracellular free Ca2+. Furthermore, STREX-deleted BKCa channels were completely insensitive to termitomycesphin A, indicating that STREX domain is required for the activation of the BKCa channel. These data provide evidence that termitomycesphins are potent in stimulating the activity of the BKCa channels. As BKCa channels are associated with pathology of many diseases, termitomycesphins might be used as therapeutic agents for treating these diseases through its regulatory effect on the BKCa channels.