Voltage-dependent Ca2+-channel block by openers of intermediate and small conductance Ca2+-activated K+ channels in urinary bladder smooth muscle cells.
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.
Morimura
Kozo
K
Department of Molecular and Cellular Pharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya 467-8603, Japan.
Yamamura
Hisao
H
Ohya
Susumu
S
Imaizumi
Yuji
Y
D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D020746:Calcium Channels, L-Type / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D051660:Intermediate-Conductance Calcium-Activated Potassium Channels / Q000187:drug effects; D015640:Ion Channel Gating; D051379:Mice; D008810:Mice, Inbred C57BL; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000378:metabolism; D010091:Oximes / Q000494:pharmacology; D051640:Small-Conductance Calcium-Activated Potassium Channels / Q000187:drug effects; D001743:Urinary Bladder / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
C507351:5,6-dichloro-1-ethyl-1,3-dihydro-2H-benzimidazol-2-one; C493327:6,7-dichloro-1H-indole-2,3-dione 3-oxime; D001562:Benzimidazoles; D020746:Calcium Channels, L-Type; D007211:Indoles; D051660:Intermediate-Conductance Calcium-Activated Potassium Channels; D010091:Oximes; D051640:Small-Conductance Calcium-Activated Potassium Channels; D002118:Calcium