Voltage-dependent Ca2+-channel block by openers of intermediate and small conductance Ca2+-activated K+ channels in urinary bladder smooth muscle cells

Abstract

We examined effects of small and intermediate conductance Ca(2+)-activated K(+) (SK and IK) channel openers, DCEBIO (5,6-dichloro-1-ethyl-1,3-dihydro-2H-benzimidazol-2-one) and NS309 (3-oxime-6,7-dichloro-1H-indole-2,3-dione), on L-type Ca(2+) channel current (I(Ca)) that was measured in smooth muscle cells isolated from mouse urinary bladder under whole cell voltage-clamp. The I(Ca) was concentration-dependently inhibited by DCEBIO and NS309; half inhibition was obtained at 71.6 and 10.6 muM, respectively. The specificity of NS309 to the IK channel over the Ca(2+) channel appears to be high and higher than that of DCEBIO. DCEBIO and even NS309 may, however, substantially block Ca(2+) channels when used as SK channel openers.