Potentiation of potassium currents by beta-adrenoceptor agonists in human urinary bladder smooth muscle cells: a possible electrical mechanism of relaxation.
We examined the effects of beta-adrenoceptor agonists on the membrane currents of smooth muscle cells from the human urinary bladder using a whole-cell patch clamp to investigate the involvement of Ca(2+)-activated K(+) (K(Ca)) channels in relaxation by beta-adrenergic agonists. With 0.05 mmol/l EGTA in the patch pipette, depolarizing pulses evoked outward rectifying currents. Isoproterenol (1 micromol/l) significantly increased the membrane currents by 75% at +80 mV with 0.05 mmol/l EGTA pipette solution. BRL 37344 (1 micromol/l) significantly increased the membrane currents by 44% at +80 mV. Iberiotoxin (100 nmol/l) significantly decreased the membrane currents by 60% at +80 mV. In the presence of iberiotoxin, the potentiation of the outward currents by isoproterenol was greatly suppressed and, in the presence of iberiotoxin and apamin (1 micromol/l), the potentiation by isoproterenol was totally abolished. On the other hand, with 5 mmol/l EGTA pipette solution, depolarizing pulses evoked smaller outward currents. Isoproterenol (1 micromol/l) did not change the membrane currents with 5 mmol/l EGTA pipette solution. The real-time PCR analysis revealed the expression of beta(2)-adrenoceptors in the cells. These results suggest that Ca(2+)-activated and iberiotoxin- and apamin-sensitive currents via both large-conductance and small-conductance K(Ca) channels could be increased by stimulation of beta(2)-adrenoceptors.
Takemoto
Jun
J
Department of Molecular Pharmacology, Graduate School of Medicine, Tohoku University, Sendai, Japan.
Masumiya
Haruko
H
Nunoki
Kazuo
K
Sato
Takeya
T
Nakagawa
Haruo
H
Ikeda
Yoshihiro
Y
Arai
Yoichi
Y
Yanagisawa
Teruyuki
T
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D001030:Apamin / Q000494:pharmacology; D002460:Cell Line; D004594:Electrophysiology; D004983:Ethanolamines / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000187:drug effects* / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism; D018408:Patch-Clamp Techniques; D010455:Peptides / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D051640:Small-Conductance Calcium-Activated Potassium Channels / Q000187:drug effects* / Q000378:metabolism; D001743:Urinary Bladder / Q000378:metabolism
D000318:Adrenergic beta-Agonists; D004983:Ethanolamines; D051036:Large-Conductance Calcium-Activated Potassium Channels; D010455:Peptides; D011943:Receptors, Adrenergic, beta; D051640:Small-Conductance Calcium-Activated Potassium Channels; D001030:Apamin; C057368:BRL 37344; C064719:iberiotoxin; D007545:Isoproterenol