Acetic acid opens large-conductance Ca 2+-activated K + channels in guinea pig detrusor smooth muscle cells

Abstract

Acetic acid was found to have actions on urinary bladder smooth muscle in our routine ion channel screening assays. Numerous studies have examined the mechanisms of bladder irritation by acetic acid; however, the direct effect of acetic acid on ion channels in detrusor smooth muscle cells has not been evaluated. We used whole-cell patch-clamp techniques to examine the effect of acetic acid on large-conductance Ca 2+-activated K + channels (BK Ca) from guinea pig detrusor smooth muscle cells and CHO cells expressing recombinant human BK Caαβ 1 (CHO BK Caαβ 1) and human BK Caα (CHO BK Caα). Acetic acid activated BK Ca currents in a concentration-dependent (0.01% to 0.05% v/v) manner in all the cell systems studied. Acetic acid (0.05%) increased BK Ca current at + 30 mV by 2764 ± 918% ( n = 8) in guinea pig detrusor smooth muscle cells. Acetic acid (0.03%) shifted the V 1/2 of conductance–voltage curve by 64 ± 14 ( n = 5), 128 ± 14 ( n = 5), and 126 ± 12 mV ( n = 4) in CHO BK Caα, CHO BK Caαβ 1 and detrusor smooth muscle cells, respectively. This effect of acetic acid was found to be independent of pH and was also not produced by its salt form, sodium acetate. Automated patch-clamp experiments also showed similar activation of CHO BK Caαβ 1 by acetic acid. In conclusion, acetic acid directly activates BK Ca channels in detrusor smooth muscle cells. This novel study necessitates caution while interpreting the results from acetic acid bladder irritation model.