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 o n the spontaneous rhythmic contractile activity were examined in guinea-pig urinary bladder smooth muscle (UBSM). Guinea-pig UBSM exhibited myogenic r hythmic contraction in the presence of atropine (1 muM), phentolamine (1 mu M), propranolol (1 muM), suramin (10 muM) and tetrodotoxin (1 muM). Nisoldi pine (100 nM) or diltiazem (10 muM) substantially diminished UBSM contracti le activity. Nisoldipine-resistant component of UBSM rhythmic contraction w as further inhibited by gadolinium (200 muM). Iberiotoxin (50 nM), a select ive blocker of large-conductance, voltage-gated Ca2+-activated K+ (K-Ca) (B K) channel, dramatically increased both contraction amplitude and frequency whereas NS-1619 (30 muM), which increases BK channel activity, decreased t hem. Apamin (100 nM), a selective blocker of small-conductance, K-Ca (SK) c hannel, increased contraction amplitude but decreased frequency. A blocker of voltage-gated K+ (K-v) channel, 4-aminopyridine (100 muM), significantly increased contraction frequency, E-4031, a blocker of a novel inwardly rec tifying K+ channel, i.e. the human ether-a-go-go-related gene (HERG) K+ cha nnel, significantly increased contraction amplitude, Glibenclamide (1-10 mu M) (K-ATP channel blocker) and Ba2+ (10 muM) (conventional K-ir channel blo cker) did not exhibit conspicuous effects on spontaneous contractile activi ty of UBSM. These findings imply that two types of Kc. (BK and SK) channels have prominent roles as negative feedback elements to limit extracellular Ca2+ influx-mediated guinea-pig UBSM contraction by regulating both amplitu de and frequency. It was also suggested that both non-K-Ca type of K+ (K-v and HERG-like K+) channels may contribute to the regulation of UBSM myogeni c rhythmic contraction.