1 In freshly-isolated single cells of the rat bladder detrusor, outwardly-rectifying and inwardlyrectifying 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). 5IIR was reduced by terikalant (100 gM) and markedly inhibited by ciclazindol (100 gM) although at these concentrations, both agents also reduced outward currents. 6 IIR was inhibited by ZD7288 (10-100 iM) in a concentration-dependent manner. At concentrations up to 30 gM, ZD7288 did not reduce the magnitude of outward currents but these were inhibited by 100 gM ZD7288. 7 In strips of bladder detrusor, spontaneous mechanical activity was increased by ZD7288 (0.3-100 gM) and by ciclazindol (0.3-100 gM) but was unaffected by glibenclamide (1-10 gM).8 It is concluded that AIR 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. Keywords: Whole-cell voltage-clamp; rat bladder detrusor; smooth muscle; inward-rectifier; Ih; ZD7288; ciclazindol; terikalant; glibenclamide; tetraethylammonium; Ba2"; Cs' Introduction Inwardly-rectifying conductances are absent from most types of smooth muscle (see Bolton & Beech, 1992). However, in the gastro-intestinal tract (rabbit jejunum: Benham et al., 1987), in certain arterioles (submucosal and cerebral: Edwards & Hirst, 1988;Quayle et al., 1993) and in guineapig detrusor (Inoue & Brading, 1990), inwardly-rectifying currents have been described.In rabbit jejunum these show some characteristics of the hyperpolarization-activated cation current (Ih) described in the cells of the sino-atrial node (DiFrancesco et al., 1986), in salamander rod photoreceptors (Wollmuth & Hille, 1992) and in a variety of neurones (Pape, 1996). Ih (Pape, 1996). In contrast, the arteriolar inwardly-rectifying current is K+-selective and is inhibited by external Ba2+ in the range 1-10 ,M (Quayle et al., 1993). In guinea-pig detrusor, neither the purinoceptor-gated nor the stretch-activated inwardly-rectifying currents exhibit selectivity for monovalent over divalent cations (Inoue & Brading, 1990).In preliminary studies, a current (VIR) with inwardly-rectifying properties has been detected in freshly-isolated smooth muscle cells from rat detrusor (Green et al., 1996). The objective of the present investigation was to determin...

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