Fig. 5.

Formoterol effects on KCNQ currents and on relaxation of rat airways: no effect on currents but enhanced bronchodilator responses when combined with retigabine. A: representative time course of KCNQ current recording in an ASMC (C = 13.9 pF) at −20 mV holding voltage before (5 min) and during treatment with formoterol fumarate (FF; 10 nM FF for 5 min). The time course recording was interrupted for 10 min for measurement of the steady-state I–V relationship (time break indicated by vertical gray lines). After an additional 5-min recording, retigabine (10 μM) was applied in the continued presence of formoterol. The time course recording was interrupted again for 10 min for recording of the steady-state I–V curves, and after an additional 5-min recording, XE991 (1 μM) was applied in the presence of retigabine. B: I–V relationships of KCNQ currents recorded in ASMCs before (control, filled circles, n = 4), during treatment with 10 nM formoterol (open circles, n = 4), in the presence of retigabine (10 μM) applied with 10 nM formoterol (open triangles, n = 3), and in the presence of XE991 (1 μM, filled triangles, n = 3). C: representative time course of changes in the lumenal area of a small airway in rat PCLS on application of 230 nM MeCh (30 min), followed by application of 230 nM MeCh in the presence of 10 nM formoterol (30 min). Dashed, vertical lines marked “max” and “final” indicate 1-min time intervals where the maximum or final relaxation was measured relative to the MeCh-induced constriction (measured during the last minute of MeCh alone). D: representative time course of changes in the lumenal area of a small airway treated as in C, except that 10 μM retigabine was included with the formoterol treatment (FF + R, 30 min). E: summarized bar graph of formoterol-induced relaxation, with or without 10 μM retigabine (gray or black bars, respectively), measured at the maximum and final time points, as indicated in C and D (n = 6–10). F: summarized bar graph of the maximum minus the final percent relaxation depicted in E. E and F: *significant difference between formoterol treatments alone vs. formoterol plus retigabine treatments (Student's t-test, n = 6–10, P < 0.05).