Pharmacological characterization of the inwardly‐rectifying current in the smooth muscle cells of the rat bladder

1 In freshly‐isolated single cells of the rat bladder detrusor, outwardly‐rectifying and inwardly‐rectifying membrane currents were identified by the whole‐cell voltage‐clamp technique. 2 The inwardly‐rectifying current (IIR) exhibited features of a cation current permeable to both K+ and Na+ but it was unaffected by changes in extracellular Ca2+. It had an activation threshold close to −60 mV and an estimated reversal potential of −29 mV. 3 IIR activated slowly with a voltage‐sensitive time‐constant of 69 ms at −140 mV and 209 ms at −100 mV but it did not exhibit time‐dependent inactivation. 4 IIR was unaffected by tetraethylammonium (up to 20 mM) but it was reduced by extracellular Ba2+(1 mM) and by extracellular Cs+ (1 mM). 5 IIR was reduced by terikalant (100 μm) and markedly inhibited by ciclazindol (100 μm) although at these concentrations, both agents also reduced outward currents. 6 IIR was inhibited by ZD7288 (10–100 μm) in a concentration‐dependent manner. At concentrations up to 30 μm, ZD7288 did not reduce the magnitude of outward currents but these were inhibited by 100 μm ZD7288. 7 In strips of bladder detrusor, spontaneous mechanical activity was increased by ZD7288 (0.3–100 μm) and by ciclazindol (0.3–100 μm) but was unaffected by glibenclamide (1–10 μm). 8 It is concluded that IIR closely resembles the hyperpolarization‐activated current, Ih, previously described in the smooth muscle of rabbit jejunum and in a variety of other cell types. This current may play an important role in modulating detrusor excitability but this could not be confirmed using the inhibitors ZD7288 and ciclazindol.