The effect of single cerebroside compounds on activation of BK_Ca channels

Abstract

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 BK_Ca channels. It is very curious to know whether a single pure cerebroside compound could activate the BK_Ca channel as well. This study explored the possible effects of pure cerebroside compounds, termitomycesphins A and B, on the BK_Ca channel activation. Both termitomycesphins A and B activated the BK_Ca channels at micromole concentration without significant difference. Termitomycesphin A increased the single channel open probability of the BK_Ca channels in a dose-dependent manner without modifying the single channel conductance. Termitomycesphin A activated BK_Ca 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 BK_Ca channels were completely insensitive to termitomycesphin A, indicating that STREX domain is required for the activation of the BK_Ca channel. These data provide evidence that termitomycesphins are potent in stimulating the activity of the BK_Ca channels. As BK_Ca 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 BK_Ca channels.

Keywords::

• BK_Ca channel
• cerebroside
• STREX domain
• termitomycesphin

Acknowledgements

We thank Dr Sokabe and Dr Naruse for their generous gift of the BK_Ca channel and its STREX-deleted form.

Declaration of interest: This work was partly supported by the National Basic Research Program of China (2005CB522804) and the National Science Foundation of China (31070741). The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.