The urethra is thought to play an important role in maintaining urinary continence by generating sufficient tone to prevent leakage of urine from the bladder. This tone is partly myogenic in nature, but can be augmented by adrenergic nerves acting on post-junctional α₁-receptors. In the present study we have examined the effects of exogenous noradrenaline on K⁺ currents in smooth muscle cells isolated from the rabbit urethra. Rabbits were killed with pentobarbitone (I.V.) and their urethras removed.

Smooth muscle cells were isolated by enzymatic dispersal and studied with the amphotericin B perforated patch technique at 37 °C using K⁺-rich pipette solutions. When cells were held at -60 mV and depolarized to 0 mV for 500 ms, a small transient inward current was evoked and this was followed by a larger transient outward current. The transient outward current was blocked by penitrem A (100 nM), suggesting that the outward current was carried through large conductance calcium-activated K⁺ (BK) channels described previously in these cells (Hollywood et al. 1999). Application of noradrenaline (10 µM) decreased the amplitude of the transient BK current from 860 ± 126 to 315 ± 60 pA (mean ± S.E.M.) and increased the amplitude of the inward current from -29 ± 21 to -48 ± 20 pA (n = 16, P < 0.05, paired t test). In the presence of the α₁ adrenoceptor antagonist prazosin (1 µM), NA failed to inhibit the BK current (574 ± 61 pA before NA compared with 563 ± 55 pA during NA, n = 5), suggesting that its effects were mediated through α₁-adrenoceptors. When calcium release from IP₃-dependent stores was blocked with 100 µM 2APB (Maruyama et al. 1997), NA failed to depress the BK current (n = 8, P > 0.5), suggesting that its effects were mediated via release of calcium from an IP₃-sensitive store.

To investigate the effect of NA on evoked action potentials, cells were studied under current clamp and brief injections of depolarizing current applied. Membrane potential was maintained at ~-60 mV by the injection of a steady backgound current. In six cells, action potentials were elicited that had a mean overshoot of 2.5 ± 3.4 mV and a duration of 42 ± 1.3 ms. In the presence of NA, the overshoot increased to 17 ± 4 mV and the duration increased to 65 ± 7 ms (n = 6, P < 0.05). These results suggest that in the presence of noradrenaline the action potential is broadened, allowing a greater influx of calcium. This may contribute to the increase in tension observed in the urethra in response to exogenous NA.

This work was supported by The Wellcome Trust and Action Research.

All procedures accord with current UK legislation.