[Effect of ipratropium bromide on calcium activated potassium channel in tracheal smooth muscle cells from chronically hypoxic rats].
OBJECTIVE
To study the effects of ipratropium bromide on large conductance calcium activated potassium (BK(Ca)) channel in tracheal smooth muscle cells (TSMC) from chronically hypoxic rat.


METHODS
The chronically hypoxic rat model was established. Single TSMC was acutely isolated. Single channel currents were recorded by using the patch clamp technique in inside-out configuration.


RESULTS
(1) Chronic hypoxia decreased BK(Ca) channel activity significantly in inside-out recording. Channel open probability (P(0)) of BK(Ca) channel in the chronically hypoxic rats reduced significantly compared with that in the control rats (0.17 +/- 0.07 for the hypoxia, 0.35 +/- 0.10 for the control, n = 30, t = 8.22, P < 0.01). Channel open time constants were significantly shortened in the chronically hypoxic group. The fast and slow open time constants (tau(O1), tau(O2))were significantly different from those in the control [tau(O1) (1.49 +/- 0.41) ms, (0.53 +/- 0.23) ms, respectively, n = 30, t = 12.07, P < 0.01; tau(O2) (11.9 +/- 3.2) ms, (3.8 +/- 1.4) ms, respectively, n = 30, t = 12.60, P < 0.01]. Closing time prolonged significantly. The fast and slow closing time constants (tau(c1), tau(c2)) were significantly different from those in the control [tau(c1) (2.7 +/- 0.9) ms, (5.7 +/- 1.5) ms, respectively, n = 30, t = 8.71, P < 0.01; tau(c2) (12.1 +/- 2.3) ms, (19.4 +/- 2.9) ms, respectively, n = 30, t = 14.05, P < 0.01]. Ipratropium bromide and salbutamol reversed the effect of chronic hypoxia on BK(Ca) channel. P(0) increased, tau(O1) and tau(O2) were prolonged significantly. tau(c1) and tau(c2) were shortened [P(0), 0.15 +/- 0.04, 0.28 +/- 0.09, 0.30 +/- 0.08, respectively, n = 25, F = 39.90, P < 0.01; tau(O1) (0.55 +/- 0.24) ms, (0.89 +/- 0.25) ms, (1.03 +/- 0.33) ms, respectively, n = 25, F = 15.32, P < 0.01; tau(O2) (3.6 +/- 1.4) ms, (6.3 +/- 1.9) ms, (6.9 +/- 2.0) ms, respectively, n = 25, F = 40.10, P < 0.01; tau(c1) (6.1 +/- 1.6) ms, (3.3 +/- 1.2) ms, (3.0 +/- 0.8) ms, respectively, n = 25, F = 57.14, P < 0.01; tau(c2) (20.1 +/- 2.5) ms, (12.4 +/- 2.6) ms, (13.0 +/- 2.0) ms, respectively, n = 25, F = 24.60, P < 0.01].


CONCLUSIONS
Chronic hypoxia decreased BK(Ca) channel activity. Ipratropium bromide and salbutamol reversed the effect of chronic hypoxia on BK(Ca) channel. The relaxing effect of ipratropium bromide and salbutamol on TSMC may be partly mediated via activation of BK(Ca) channel.
Luo
Yaling
Y
Department of Respiratory Disease, Nanfang Hospital, Guangzhou 510515, China.
Cheng
Shihu
S
Lai
Wenyan
W
Luo
Liang
L
D000818:Animals; D001993:Bronchodilator Agents / Q000494:pharmacology*; D000860:Hypoxia / Q000503:physiopathology*; D009241:Ipratropium / Q000494:pharmacology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009130:Muscle, Smooth / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D018408:Patch-Clamp Techniques; D024681:Potassium Channels, Calcium-Activated / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D014132:Trachea / Q000166:cytology / Q000187:drug effects / Q000502:physiology
D001993:Bronchodilator Agents; D024681:Potassium Channels, Calcium-Activated; D009241:Ipratropium