title: Acetic acid opens large-conductance Ca2+-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 Ca2+-activated K+ channels (BKCa) from guinea pig detrusor smooth muscle cells and CHO cells expressing recombinant human BKCaalphabeta1 (CHO BKCaalphabeta1) and human BKCaalpha (CHO BKCaalpha). Acetic acid activated BKCa currents in a concentration-dependent (0.01% to 0.05% v/v) manner in all the cell systems studied. Acetic acid (0.05%) increased BKCa current at +30 mV by 2764+/-918% (n=8) in guinea pig detrusor smooth muscle cells. Acetic acid (0.03%) shifted the V1/2 of conductance-voltage curve by 64+/-14 (n=5), 128+/-14 (n=5), and 126+/-12 mV (n=4) in CHO BKCaalpha, CHO BKCaalphabeta1 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 BKCaalphabeta1 by acetic acid. In conclusion, acetic acid directly activates BKCa channels in detrusor smooth muscle cells. This novel study necessitates caution while interpreting the results from acetic acid bladder irritation model.
authors: Department of Pharmaceutical Sciences, College of Pharmacy, North Dakota State University, Fargo ND 58105, USA.
authors: Srinivas
authors: S
authors: Ghatta
authors: Irina
authors: I
authors: Lozinskaya
authors: Zuojun
authors: Z
authors: Lin
authors: Earl
authors: E
authors: Gordon
authors: Robert N
authors: RN
authors: Willette
authors: David P
authors: DP
authors: Brooks
authors: Xiaoping
authors: X
authors: Xu
mesh_terms: D019342:Acetic Acid / Q000494:pharmacology*; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D006801:Humans; D066298:In Vitro Techniques; D007509:Irritants / Q000494:pharmacology*; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D051038:Large-Conductance Calcium-Activated Potassium Channel beta Subunits / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000378:metabolism; D018408:Patch-Clamp Techniques; D011994:Recombinant Proteins / Q000819:agonists; D014162:Transfection; D001743:Urinary Bladder / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
chemical_list: D007509:Irritants; C494841:KCNMA1 protein, human; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; D051038:Large-Conductance Calcium-Activated Potassium Channel beta Subunits; D011994:Recombinant Proteins; D019342:Acetic Acid