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 ( I IR ) exhibited features of a cation current permeable to both K + and Na + but it was unaffected by changes in extracellular Ca 2+ . It had an activation threshold close to −60 mV and an estimated reversal potential of −29 mV. 3 I IR 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 I IR was unaffected by tetraethylammonium (up to 20 mM) but it was reduced by extracellular Ba 2+ (1 mM) and by extracellular Cs + (1 mM). 5 I IR was reduced by terikalant (100 μ m ) and markedly inhibited by ciclazindol (100 μ m ) although at these concentrations, both agents also reduced outward currents. 6 I IR was inhibited by ZD7288 (10–100 μ m ) in a concentration‐dependent manner. At concentrations up to 30 μ m , ZD7288 did not reduce the magnitude of outward currents but these were inhibited by 100 μ m ZD7288. 7 In strips of bladder detrusor, spontaneous mechanical activity was increased by ZD7288 (0.3–100 μ m ) and by ciclazindol (0.3–100 μ m ) but was unaffected by glibenclamide (1–10 μ m ). 8 It is concluded that I IR closely resembles the hyperpolarization‐activated current, I h , 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.