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 Ca²⁺-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 Ca²⁺ 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 μM, respectively. The specificity of NS309 to the IK channel over the Ca²⁺ channel appears to be high and higher than that of DCEBIO. DCEBIO and even NS309 may, however, substantially block Ca²⁺ channels when used as SK channel openers.