TY - JOUR AU - Liu Xian-Sheng AU - Xu Yong-Jian AU - Zhang Zhen-Xiang AU - Li Chao-Qian AU - Yang Dan-Lei AU - Zhang Ning AU - Ni Wang PY - 2016 TI - Isoprenaline and aminophylline relax bronchial smooth muscle by cAMP-induced stimulation of large-conductance Ca2+-activated K+ channels. JF - Acta Pharmacologica Sinica; Vol 24, No 5 (May 2003): Acta Pharmacologica Sinica Y2 - 2016 KW - N2 - AIM: 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. CONCLUSION: The relaxations induced by isoprenaline and aminophylline were, at least partly, mediated by cAMP-stimulation of BK(Ca) in rat bronchial smooth muscle. UR - http://www.chinaphar.com/article/view/9106