Sensitivity of epinephrine-activated K+ secretion to combined K+ channel blockers. Adjacent mucosae were pretreated with the β2-adrenergic receptor antagonist ICI-118551 (1.0 μM) added to the serosal solution 30 min prior to epinephrine (5 μM) stimulation. A: 2 of 4 mucosae were pretreated with mucosally added paxilline 55 min prior to epinephrine, at either 1.0 μM (dotted line) or 10 μM (dashed line). After maximal activation, IbTx (300 nM) was added mucosally to control (gray solid line) and 1.0 μM paxilline pretreated mucosae (asterisks). A control mucosa without channel inhibitors is shown (black solid line). Combined IbTx/pax fractional inhibition was 0.77 compared with maximal inhibition (10 μM paxilline), exceeding the expectation of 0.67 for independent inhibitor actions. B: 2 of 3 mucosae were pretreated mucosally with paxilline 60 min prior to epinephrine, at either 1.0 μM (dotted line) or 10 μM (dashed line). After maximal activation ChTx (300 nM) was added mucosally to control (solid line) and 1.0 μM paxilline-pretreated mucosae (asterisk). Combined ChTx/pax fractional inhibition was 0.74 compared with 10 μM paxilline, exceeding the expectation of 0.49 for independent inhibitor actions. C and D: 2 of 3 mucosae were pretreated with paxilline 50 min prior to epinephrine, at either 1.0 μM mucosal and serosal (dotted line) or 10 μM mucosal (dashed line). After maximal activation, either Tram34 (100 μM) or BaCl2 (10 mM) was added mucosally to control (solid line) and paxilline-pretreated mucosae (asterisks).