A comparison of the effects of SCA40, NS 004 and NS 1619 on large conductance Ca(2+)-activated K+ channels in bovine tracheal smooth muscle cells in culture.
1. The effects of imidazopyrazine derivative, SCA40, on the activity of single large conductance, Ca(2+)-activated K+ (BKCa) channels in inside-out and outside-out patches from bovine tracheal smooth muscle (BTSM) cells in culture have been compared with those of two established BKCa channel openers, NS 004 and NS 1619. 2. The presence of BKCa channels on inside-out patches of BTSM membranes was confirmed by the single channel conductance (240 pS), selectivity for K+, dependence of channel activity on [Ca2+]i, and sensitivity to the selective BKCa channel blocker, iberiotoxin. 3. NS 004 and ND 1619 (3-30 microM) induced concentration-related increases in open state probability of BKCa channels when applied to either inside-out or outside-out BTSM patches, thus confirming that these compounds are activators of the BKCa channel in this preparation. 4. SCA40 (0.1-10 microM) had no effect on the activity of BKCa channels when applied to either inside-out or outside-out patches which subsequently responded to the application of NS 004 (10-20 microM). 5. It is concluded that SCA40 does not have a direct effect on BKCa channel activity in BTSM patches and that the previously reported relaxant action of SCA40 on tracheal smooth muscle is unlikely to be mediated by this mechanism.
Macmillan
S
S
Department of Pharmacology, Syntex Research Centre, Riccarton, Edinburgh.
Sheridan
R D
RD
Chilvers
E R
ER
Patmore
L
L
D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology*; D002118:Calcium / Q000502:physiology*; D002417:Cattle; D002478:Cells, Cultured; D002733:Chlorophenols / Q000494:pharmacology*; D004553:Electric Conductivity; D007093:Imidazoles / Q000494:pharmacology*; D066298:In Vitro Techniques; D015640:Ion Channel Gating / Q000187:drug effects*; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D010276:Parasympatholytics / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects* / Q000502:physiology; D011719:Pyrazines / Q000494:pharmacology*; D014132:Trachea / Q000187:drug effects* / Q000502:physiology
D001562:Benzimidazoles; D002733:Chlorophenols; D007093:Imidazoles; D010276:Parasympatholytics; D015221:Potassium Channels; D011719:Pyrazines; C080660:6-bromo-8-methylaminoimidazo(1,2-a)pyrazine-2-carbonitrile; C086491:NS 1619; C083230:NS 004; D002118:Calcium