Effects of different types of K+ channel modulators on the spontaneous myogenic contraction of guinea-pig urinary bladder smooth muscle.

In the present study, effects of different types of K+ channel modulators on the spontaneous rhythmic contractile activity were examined in guinea-pig urinary bladder smooth muscle (UBSM). Guinea-pig UBSM exhibited myogenic rhythmic contraction in the presence of atropine (1 microM), phentolamine (1 microM), propranolol (1 microM), suramin (10 microM) and tetrodotoxin (1 microM). Nisoldipine (100 nM) or diltiazem (10 microM) substantially diminished UBSM contractile activity. Nisoldipine-resistant component of UBSM rhythmic contraction was further inhibited by gadolinium (200 microM). Iberiotoxin (50 nM), a selective blocker of large-conductance, voltage-gated Ca2+-activated K+ (K(Ca)) (BK) channel, dramatically increased both contraction amplitude and frequency whereas NS-1619 (30 microM), which increases BK channel activity, decreased them. Apamin (100 nM), a selective blocker of small-conductance, K(Ca) (SK) channel, increased contraction amplitude but decreased frequency. A blocker of voltage-gated K+ (Kv) channel, 4-aminopyridine (100 microM), significantly increased contraction frequency. E-4031, a blocker of a novel inwardly rectifying K+ channel, i.e. the human ether-a-go-go-related gene (HERG) K+ channel, significantly increased contraction amplitude. Glibenclamide (1-10 microM) (K(ATP) channel blocker) and Ba2+ (10 microM) (conventional K(ir) channel blocker) did not exhibit conspicuous effects on spontaneous contractile activity of UBSM. These findings imply that two types of K(Ca) (BK and SK) channels have prominent roles as negative feedback elements to limit extracellular Ca2+ influx-mediated guinea-pig UBSM contraction by regulating both amplitude and frequency. It was also suggested that both non-K(Ca) type of K+ (Kv and HERG-like K+) channels may contribute to the regulation of UBSM myogenic rhythmic contraction.