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 Ca(2+)-dependent activation curve of the channel upwards, suggesting that termitomycesphin A could activate the channels even without intracellular free Ca(2+). 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.
journal_name
Mol Membr Bioljournal_title
Molecular membrane biologyauthors
Xu H,Qi J,Wang G,Deng H,Qi Zdoi
10.3109/09687688.2010.538731subject
Has Abstractpub_date
2011-02-01 00:00:00pages
145-54issue
2eissn
0968-7688issn
1464-5203journal_volume
28pub_type
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