Involvement of BK(Ca) channels in the relaxation of detrusor muscle via beta-adrenoceptors.
Detrusor muscle relaxes upon activation of beta-adrenoceptors on smooth muscle cells. However, the mechanism of relaxation following the stimulation of beta-adrenoceptors remains unclear. In order to clarify the mechanism, we investigated the involvement of ion channels in bladder relaxation. In guinea-pig isolated bladder strips precontracted by high-K(+), isoproterenol caused concentration-dependent relaxation. The relaxation caused by isoproterenol (1 microM) was larger in 30 mM K(+) than in 120 mM K(+) (54.2+/-8.0% and 18.2+/-4.1% of papaverine-induced relaxation, respectively, n=4). Iberiotoxin (100 nM) inhibited the isoproterenol-induced relaxation (vehicle 69.5+/-8.0% vs. iberiotoxin 24.9+/-6.2%, respectively, n=5). Whole-cell patch-clamp recording revealed that isoproterenol as well as forskolin increased the iberiotoxin-sensitive K(+) currents, and this increase was abolished by protein kinase inhibitor. These results suggest that the isoproterenol-induced relaxation of guinea-pig bladder smooth muscle is mainly mediated by facilitation of BK(Ca) channels subsequent to the activation of the cAMP/protein kinase A pathway.
Kobayashi
H
H
Laboratory of Pharmacology and Toxicology, Graduate School of Pharmaceutical Sciences, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, 113-0033, Tokyo, Japan.
Adachi-Akahane
S
S
Nagao
T
T
D000818:Animals; D006168:Guinea Pigs; D066298:In Vitro Techniques; D051036:Large-Conductance Calcium-Activated Potassium Channels; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D009126:Muscle Relaxation / Q000502:physiology*; D009130:Muscle, Smooth / Q000166:cytology / Q000502:physiology*; D015221:Potassium Channels / Q000502:physiology*; D024681:Potassium Channels, Calcium-Activated; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D001743:Urinary Bladder / Q000166:cytology / Q000502:physiology
D051036:Large-Conductance Calcium-Activated Potassium Channels; D015221:Potassium Channels; D024681:Potassium Channels, Calcium-Activated; D011943:Receptors, Adrenergic, beta