Abstract
Silver has been widely used in various medical products due to its antibacterial properties. However, there is only limited information concerning silver-related cytotoxicity. In this study we show that Ag+ at low nanomolar concentrations (< 10 nM) strongly inhibits the activity of BK channels (Slo1), a widely expressed and physiologically important potassium channel. The Ag+ inhibition is caused by irreversible modification on cytosolically accessible parts of the BK channel. At least four intracellular cysteines are involved in this process. In addition, at least one of these key cysteines is not accessible to the bulkier thiolate-active reagent MTSET. One of the cys-less construct generated in this study shows gating properties similar to wild type BK channel, but with much lower Ag+ sensitivity, in which the Ag+ modification rate was decreased by about 20-fold. The results from the present study suggest a possible contribution of BK channel inhibition to the cytotoxicity of Ag+ in humans and other species.
Footnotes
- Received May 14, 2010.
- Revision received August 19, 2010.
- Accepted August 20, 2010.
- The American Society for Pharmacology and Experimental Therapeutics