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 β-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 Ca²⁺- activated K⁺ (K_Ca) channels in relaxation by β-adrenergic agonists. With 0.05 mmol/l EGTA in the patch pipette, depolarizing pulses evoked outward rectifying currents. Isoproterenol (1 μmol/l) significantly increased the membrane currents by 75% at +80 mV with 0.05 mmol/l EGTA pipette solution. BRL 37344 (1 μmol/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 μmol/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 μmol/l) did not change the membrane currents with 5 mmol/l EGTA pipette solution. The real-time PCR analysis revealed the expression of β₂-adrenoceptors in the cells. These results suggest that Ca²⁺-activated and iberiotoxin- and apamin-sensitive currents via both large-conductance and small-conductance K_Ca channels could be increased by stimulation of β₂-adrenoceptors.