Abstract
1. Single smooth muscle cells were isolated freshly from the rabbit portal vein and membrane currents were recorded by the whole-cell or excised patch configurations of the patch-clamp technique at room temperature. 2. Cromakalim (Ckm, 10 microM) induced a potassium current (ICkm) that showed no pronounced voltage-dependence and had low current noise. 3. This current, ICkm, was inhibited by (in order of potency): phencyclidine greater than quinidine greater than 4-aminopyridine greater than tetraethylammonium ions (TEA). These drugs inhibited the delayed rectifier current, IdK, which is activated by depolarization of the cell, with the same order of potency. 4. Large conductance calcium-activated potassium channels (LKCa) in isolated membrane patches were blocked by (in order of potency) quinidine greater than TEA approximately phencyclidine. 4-Aminopyridine was ineffective. A similar order of potency was found for block of spontaneous transient outward currents thought to represent bursts of openings of LKCa channels. 5. The low current noise of ICkm at positive potentials, and its susceptibility to inhibitors indicated that it was not carried by LKCa channels, and that it may be carried by channels which underlie IdK. It was observed that when ICkm was activated, IdK was reduced. However, in two experiments, ICkm was much more susceptible to glibenclamide than IdK; possible reasons for this are discussed.
MeSH Terms
Animals
Benzopyrans/pharmacology
Calcium/metabolism
Cromakalim
In Vitro Techniques
Indicators and Reagents
Kinetics
Membrane Potentials/drug effects
Muscle, Smooth, Vascular/cytology,metabolism
Parasympatholytics/pharmacology
Portal Vein/cytology,drug effects,metabolism
Potassium Channels/drug effects
Pyrroles/pharmacology
Rabbits
Chemicals
Benzopyrans
Indicators and Reagents
Parasympatholytics
Potassium Channels
Pyrroles
Cromakalim
Calcium
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Beech D J
Department of Pharmacology & Clinical Pharmacology, St. George's Hospital Medical School, London.
Bolton T B
References (29)
29 references, click to expand
-
Modification of K+ conductance of heart cell membrane by BRL 34915.
Naunyn Schmiedebergs Arch Pharmacol. 1988 Jan;337(1):93-7
PMID: 3368016
-
Adenosine 5'-triphosphate-sensitive potassium channels.
Annu Rev Neurosci. 1988;11:97-118
PMID: 2452599
-
Actions of BRL 34915 (Cromakalim) upon convulsive discharges in guinea pig hippocampal slices.
Naunyn Schmiedebergs Arch Pharmacol. 1988 Apr;337(4):429-34
PMID: 3405317
-
The pharmacology of potassium channels and their therapeutic potential.
Trends Pharmacol Sci. 1988 Jan;9(1):21-8
PMID: 3072727
-
A voltage-dependent outward current with fast kinetics in single smooth muscle cells isolated from rabbit portal vein.
J Physiol. 1989 May;412:397-414
PMID: 2600838
-
Muscarinic suppression of a novel voltage-sensitive K+ current in a vertebrate neurone.
Nature. 1980 Feb 14;283(5748):673-6
PMID: 6965523
-
Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches.
Pflugers Arch. 1981 Aug;391(2):85-100
PMID: 6270629
-
Patch-clamp studies of slow potential-sensitive potassium channels in longitudinal smooth muscle cells of rabbit jejunum.
J Physiol. 1983 Jul;340:469-86
PMID: 6310100
-
ATP-regulated K+ channels in cardiac muscle.
Nature. 1983 Sep 8-14;305(5930):147-8
PMID: 6310409
-
Intracellular ATP directly blocks K+ channels in pancreatic B-cells.
Nature. 1984 Sep 20-26;311(5983):271-3
PMID: 6090930
-
The sulphonylurea receptor may be an ATP-sensitive potassium channel.
Lancet. 1985 Aug 31;2(8453):474-5
PMID: 2412077
-
Cholinergic agonists suppress a potassium current in freshly dissociated smooth muscle cells of the toad.
J Physiol. 1985 Oct;367:503-29
PMID: 2414443
-
Two Ca-dependent K-channels classified by the application of tetraethylammonium distribute to smooth muscle membranes of the rabbit portal vein.
Pflugers Arch. 1985 Oct;405(3):173-9
PMID: 2415914
-
Kinetics of veratridine action on Na channels of skeletal muscle.
J Gen Physiol. 1986 Jan;87(1):1-24
PMID: 2419478
-
A newly identified Ca2+ dependent K+ channel in the smooth muscle membrane of single cells dispersed from the rabbit portal vein.
Pflugers Arch. 1986 Feb;406(2):138-43
PMID: 2421236
-
Calcium-activated potassium channels in single smooth muscle cells of rabbit jejunum and guinea-pig mesenteric artery.
J Physiol. 1986 Feb;371:45-67
PMID: 2422353
-
Comparison of the effects of BRL 34915 and verapamil on electrical and mechanical activity in rat portal vein.
Br J Pharmacol. 1986 May;88(1):103-11
PMID: 3708211
-
Effect of apamin on responses to BRL 34915, nicorandil and other relaxants in the guinea-pig taenia caeci.
Br J Pharmacol. 1986 May;88(1):113-20
PMID: 2423171
-
The effects of BRL 34915 and nicorandil on electrical and mechanical activity and on 86Rb efflux in rat blood vessels.
Br J Pharmacol. 1986 May;88(1):121-8
PMID: 2423172
-
Electrical and mechanical effects of BRL34915 in guinea-pig isolated trachealis.
Br J Pharmacol. 1986 Oct;89(2):395-405
PMID: 2430658
-
Identification of two toxins from scorpion (Leiurus quinquestriatus) venom which block distinct classes of calcium-activated potassium channel.
FEBS Lett. 1986 Dec 1;209(1):117-21
PMID: 2433153
-
Modulation of ionic currents in smooth muscle balls of the rabbit intestine by intracellularly perfused ATP and cyclic AMP.
Pflugers Arch. 1987 May;408(5):465-73
PMID: 2439980
-
Effect of the K+ efflux stimulating vasodilator BRL 34915 on 86Rb+ efflux and spontaneous activity in guinea-pig portal vein.
Br J Pharmacol. 1987 Jul;91(3):569-78
PMID: 3038244
-
Spontaneous transient outward currents in single visceral and vascular smooth muscle cells of the rabbit.
J Physiol. 1986 Dec;381:385-406
PMID: 2442353
-
Specificity of action of the novel antihypertensive agent, BRL 34915, as a potassium channel activator. Comparison with nicorandil.
Biochem Pharmacol. 1987 Nov 1;36(21):3663-9
PMID: 2445348
-
Maitotoxin-activated single calcium channels in guinea-pig cardiac cells.
Br J Pharmacol. 1987 Nov;92(3):665-71
PMID: 2447990
-
Regulation of calcium current by intracellular calcium in smooth muscle cells of rabbit portal vein.
Circ Res. 1988 Feb;62(2):375-83
PMID: 2448060
-
The effects of tetraethylammonium ions, 4-aminopyridine or quinidine on K+-currents in single smooth muscle cells of the rabbit portal vein.
Biomed Biochim Acta. 1987;46(8-9):S673-6
PMID: 2449198
-
Antidiabetic sulfonylureas control action potential properties in heart cells via high affinity receptors that are linked to ATP-dependent K+ channels.
J Biol Chem. 1988 Jun 15;263(17):7933-6
PMID: 2453509