1台北市立聯合醫院 泌尿科；2慈濟大學醫學系 泌尿科，3台灣大學醫學系 泌尿科
Chloride channels are involved in the regulation of bladder smooth muscle tone in rats.
Yuh-Chen Kuo1,2, Ju-Ton Hseih3
Department of Urology1, Taipei City Hospital, Taipei, Taiwan; Department of Urology2, School of Medicine, Buddhist Tzu Chi University, Hualien, Taiwan; Department of Urology3, School of Medicine, National University, Taipei, Taiwan
Purpose: Ion channels have been proved to be of functional importance in the regulation of bladder smooth muscle (SM) tone. The role of chloride channels on the bladder SM tissue has not been elucidated. We investigated the physiological roles of CLC-3 chloride channel and calcium-activated chloride channel (CaCC) on the maintenance of bladder SM tone in isolated rat bladder tissues.
Materials and Methods: Bladder smooth muscle tissue strips (2 x 2 x 10 mm) were suspended in tissue bath chambers for isometric tension experiments. Contractions elicited by KCl were examined in the condition of changing concentration of extracellular chloride (ECl) from 138 mM to 8 mM and substitution of extracellular Cl- to Br- or I-. Contractions elicited by norepinephrine (NE) were examined in the presence of chloride transport inhibitors: bumetanide (BUM), 4-(2-hydroxyethyl)-1-1- piperazine ethanesulphonic acid (HEPES) without bicarbonate, ethacrynic acid (ETH), and chloride channel blockers: 4,4'-diisothiocyano-2,2'-stilbene-disulfonic acid (DIDS), anthracene-9-carboxylic acid (A9C) and niflumic acid (NFA) (All concentration: 10^-8M~1M).
Results: In bladder SM strips the KCl induced contractility decreased significantly as the concentration of ECl changed from 138 to 8 mM (p<0.01, figure 1). The KCl elicited contractile response also decreased significantly as the extracellular Cl- was substituted by Br- or I- (p<0.01, figure 2). In addition, pretreatment with BUM, HEPES or ETH could significantly suppress the NE induced contractility in a concentration dependent manner (all p<0.01, figure 3). Pretreatment with DIDS, A9C or NFA could also significantly reduce the NE elicited contractile response in a concentration dependent manner (all p<0.01, figure 4).
Conclusions: Our results imply that both CLC-3 chloride channel and CaCC are of functional importance in the regulation of bladder smooth muscle tone.