Isoprenaline and aminophylline relax bronchial smooth muscle by cAMP-induced stimulation of large-conductance Ca2+-activated K+ channels.
OBJECTIVE
To investigate whether the relaxation of bronchial smooth muscle induced by isoprenaline and aminophylline is mediated by large conductance Ca2+-activated K+ channels (BK(Ca)) via cAMP-dependent mechanism.


METHODS
With isometric tension recording, the role of BK(Ca) in relaxations of rat bronchial strips induced by isoprenaline and aminophylline was determined. With perforated patch-clamp technique, BK(Ca) currents were observed in freshly isolated rat bronchial myocytes.


RESULTS
Tetraethylammonium 5 mmol/L, a BK(Ca) blocker, caused a significant rightward shift in the concentration-response curves of isoprenaline and aminophylline (about 4.26-fold and 3.78-fold, respectively) in methacholine-precontracted rat bronchial strips. Isoprenaline 1 micromol/L caused a significant increase in BK(Ca) current from (94+/-15) pA/pF to (186+/-30) pA/pF (voltage steps from -60 mV to +50 mV, n=10, P<0.01), which was partly abolished by Rp-cAMP 100 micromol/L, a protein kinase A inhibitor. Furthermore, current-voltage relationship(I-V) curve exhibited an upward shift, and the peak current density was significantly raised (n=10, P<0.01) by ramp depolarization from -100 mV to +100 mV. Aminophylline 1 mmol/L caused a significant increase in BK(Ca) current from (90+/-10) pA/pF to (166+/-25) pA/pF (voltage steps from -60 mV to +50 mV, n=11, P<0.01), which was partly abolished by Rp-cAMP 100 micromol/L. Furthermore, the I-V curve exhibited an upward shift, and the peak current density was significantly raised (n=11, P<0.01) by ramp depolarization from -100 mV to +100 mV.


CONCLUSIONS
The relaxations induced by isoprenaline and aminophylline were, at least partly, mediated by cAMP-stimulation of BK(Ca) in rat bronchial smooth muscle.
Department of Respiratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. liu_xiansheng@hotmail.com
Xian-Sheng
XS
Liu
Yong-Jian
YJ
Xu
Zhen-Xiang
ZX
Zhang
Chao-Qian
CQ
Li
Dan-Lei
DL
Yang
Ning
N
Zhang
Wang
W
Ni
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000628:Aminophylline / Q000494:pharmacology*; D000818:Animals; D001980:Bronchi / Q000187:drug effects*; D001993:Bronchodilator Agents / Q000494:pharmacology*; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D024681:Potassium Channels, Calcium-Activated / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D001993:Bronchodilator Agents; D024681:Potassium Channels, Calcium-Activated; D015124:8-Bromo Cyclic Adenosine Monophosphate; D000628:Aminophylline; D007545:Isoproterenol