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Fig. 3 | Respiratory Research

Fig. 3

From: Bitter taste receptor agonists regulate epithelial two-pore potassium channels via cAMP signaling

Fig. 3

Denatonium benzoate-induced current changes occur through K2P channels. Representative Ussing chamber current tracings of human sinonasal ALI cultures treated with 2 mM denatonium benzoate (D) and various combinations of apical K2P channel blockers (bupivacaine (B), 0.2 mM) or basolateral potassium channel blockers (30 µM clofilium and 100 µM clotrimazole (C/C)). All cultures were initially treated with 10 µM amiloride to block ENaC, and at the end of the experiment with 10 µM Inh172 and 100 µM IBMX/10 µM Forskolin (I/F). a Cultures treated with (solid line) apical 0.2 mM bupivacaine (K2P channel blocker) have a diminished response to denatonium. b Basolateral potassium channel blockers pre (solid line) or post (dashed line) denatonium treatment do not affect denatonium-induced Isc. c Summary data demonstrating a significant (p < 0.0001) decrease in denatonium-benzoate induced Isc with bupivacaine pretreatment but not clofilium and clotrimazole pre-treatment. d Representative Ussing chamber current tracing of cultures treated with a combination of apical K2P channel blocker and basolateral potassium channel blockers. e Summary data demonstrating a significant (p = 0.0013) reduction in I/F-mediated reversal of the denatonium-induced current changes with pre-treatment with the combination of apical bupivacaine and basolateral clofilium/clotrimazole. There is a non-significant trend toward reduction of I/F-mediated current changes with apical bupivacaine or basolateral clofilium/clotrimazole pretreatment. Shown in Panel C and E are the individual data points, mean and standard error of the mean

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