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At least 577 records · Page 32Linked to original sources
PubMed2001

Influence of ATP-sensitive K+ channel modulation on the mechanical properties of diabetic myocardium.

ATP-sensitive K+ (KATP) channels are therapeutic targets for hypertension and diabetes. KATP channel opening elicits vasorelaxation and myocardial protection, whereas its closing stimulates insulin secretion. The cardiac KATP conductance is believed altered under diabetes. This study was to evaluate the influence of KATP channel openers and blocker on myocardial contractile dysfunction in diabetes. Adult rats were made diabetic with streptozotocin (55 mg/kg) and maintained for eight weeks. Contractile properties were studied using isolated papillary muscles in the absence or presence of KATP channel openers (BRL 38227 and pinacidil) and KATP blocker (glyburide). Experimental diabetes led to hyperglycemia, reduced growth, cardiac hypertrophy and hepatomegaly. Mechanical properties exhibited prolonged duration and reduced velocity of both contraction and relaxation in diabetic myocardium, characteristic of diabetic cardiomyopathy. Acute exposure to both KATP channel openers induced concentration-dependent negative inotropic effects (NIE) on myocardial contraction. The magnitude of the NIE was similar between the normal and diabetic groups and was fully reversible upon washout for BRL 38227 although not for pinacidil. Both KATP channel openers depressed the velocity of contraction and relaxation, whereas exerted no effect on the duration of contraction and relaxation, in myocardium from both groups. Acute exposure to glyburide, a KATP channel blocker, failed to alter any of the mechanical parameters measured. These data suggest that acute modulation of KATP channel with channel opener or blocker had little influence on diabetic cardiomyopathy, at least in the setting of multicellular preparations.

Adenosine Triphosphate↗
PubMed2003

Effects of L-type Ca(2+)-channel blockade, K(+)(ATP)-channel opening and nitric oxide on human uterine contractility in relation to gestational age and labour.

Relative uterine inactivity during pregnancy changes to vigorous rhythmic contractility during labour. We hypothesized that mechanisms involved in the regulation of uterine quiescence and contractility differ between term and preterm myometrium and in labour and non-labour states. Myometrial strips, prepared from biopsies taken at Caesarean section from labouring and non-labouring women preterm and at term, were mounted in organ chambers for isometric tension recording. Oxytocin (10(-9) mol/l) was added to maintain stable contractions, and effects of various inhibitors of uterine contractility were studied. The inhibitory effects of L-type Ca(2+)-channel blocker nifedipine and ATP-sensitive K(+)-channel opener pinacidil were greater in myometrium from the non-labour versus the labour group, both preterm and at term. In addition, pinacidil's effect was greater at term compared with preterm in the non-labour group. Mg(2+) and the nitric oxide donor sodium nitroprusside significantly inhibited contractility in all groups without significant differences with regard to labour or gestational age. Decreased inhibition of human uterine contractility by L-type Ca(2+)-channel blockers and K(+)(ATP)-channel openers in preterm and term labour may reflect changes in expression and activity of these channels. Effects of nitric oxide and Mg(2+) are not affected by gestational age or labour.

Adult↗
PubMed1992

ATP-sensitive potassium channel agonists do not alter MAC for isoflurane in rats.

The molecular mechanisms for general anesthesia are probably restricted to a sensitive set of target sites in the brain. Membrane hyperpolarization, brought about by increased potassium channel conductance, is coupled to opiate mu receptors, to alpha 2- adrenoceptors, and to muscarinic M2 receptors, all of which have anesthetic-sparing effects. One type of potassium channel, the ATP-sensitive potassium channel (IKATP) has well-known agonists: cromakalim and pinacidil. The effects on isoflurane minimum alveolar concentration (MAC) of intracerebroventricular injection of these IKATP agonists and of the alpha 2-adrenoceptor agonist clonidine were studied in rats. Baseline MAC was 1.60% (+/- 0.02 SEM) isoflurane in oxygen. 10 micrograms clonidine decreased MAC by 42% of baseline (P less than 0.05); 20 micrograms clonidine decreased MAC by 58% of baseline (P less than 0.01). Neither cromakalim (20 micrograms) nor pinacidil (20 micrograms) had any effect on MAC. The results imply that neither indiscriminate agonist action of volatile anesthetics at potassium channels nor indiscriminate inhibitory membrane hyperpolarization is likely to be a fundamental mechanism of anesthesia. Furthermore, potassium channels coupled to opiate mu receptors, to alpha 2 adrenoceptors, and to muscarinic M2 receptors are probably not the IKATP type.

Animals↗
PubMed1996

Coronary vascular ATP-sensitive potassium channels are activated to a greater extent in spontaneously hypertensive rats than in Wistar-Kyoto rats.

OBJECTIVE: To determine whether opening of coronary vascular adenosine 5'-triphosphate (ATP)-sensitive potassium (KATP) channels is involved in the maintenance of resting coronary flow in hypertrophied hearts. METHODS: We examined the effects of glibenclamide, a selective inhibitor of KATP channels, on basal coronary vascular tone in Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHRs). Using a Langendorff system, the hearts from WKY rats and SHRs were isolated and perfused with oxygenated Krebs-Henseleit solution at a constant perfusion pressure of 60 and 100 mmHg respectively. RESULTS: Basal coronary flow and myocardial oxygen consumption (MV02) were similar in SHRs and WKY rats. The percentage decreases in coronary flow with glibenclamide at graded doses were greater (P < 0.01) in SHRs than in WKY rats (n = 8), whereas the percentage decreases in MV02 with glibenclamide were similar in the two groups. The decreases in coronary flow caused by U46619 (a thromboxane A2-mimetic agent) were similar in SHRs and WKY rats (n = 4). The increase in coronary flow caused by pinacidil (a KATP opener) was greater in SHRs than in WKY rats; glibenclamide prevented the pinacidil-induced increase in coronary flow in both SHRs and WKY rats. There was a significant positive correlation between the glibenclamide-induced decrease in coronary flow and the degree of left ventricular hypertrophy (r = 0.54, P < 0.05). CONCLUSION: Our results suggest that the basal opening state of coronary vascular KATP channels is activated to a greater extent in SHRs than WKY rats, which may contribute to the maintenance of basal myocardial perfusion in hypertrophied hearts.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1998

Temperature-sensitive effects of potassium channel openers on isolated guinea pig myocardium and aorta.

The effects of K+ channel openers, NIP-121, cromakalim, and pinacidil, on isolated myocardium and aorta were investigated at two different temperatures, 23 degrees C and 37 degrees C. In right ventricular myocardium, NIP-121 shortened the action-potential duration with little influence on other action-potential parameters at 37 degrees C, but not at 23 degrees C. In whole-cell clamped ventricular myocytes, NIP-121 induced a glibenclamide-sensitive outward current at 37 degrees C but not at 23 degrees C. No difference in tissue adenosine triphosphate (ATP) concentration was detected between ventricular myocardia incubated at 37 degrees C and at 23 degrees C. In aortic preparations precontracted with norepinephrine, NIP-121, cromakalim, and pinacidil produced endothelium-independent relaxation at 37 degrees C, which was antagonized by glibenclamide. The vasorelaxant effects were greatly reduced at 23 degrees C. Thus we demonstrated that the effects of K+ channel openers on the myocardium and vascular smooth muscle are temperature sensitive.

Action Potentials↗
PubMed1990

Effects of N-(2-hydroxyethyl)nicotinamide nitrate (nicorandil; SG-75) and its derivatives on pancreatic exocrine secretion in the dog.

Nicorandil, a compound containing a nitrate moiety, can act as a K+ channel opener. Previously we reported stimulatory effects of an intraarterial injection of nicorandil on pancreatic exocrine secretion in the isolated, blood-perfused pancreas under a constant perfusion pressure. To clarify this mechanism in relation to the chemical structure we studied the effects of nicorandil and its derivatives [nitrate containing structure, N-(3-hydroxy-propyl)nicotinamide nitrate (SG-89); nitrate lacking structure, N-(2-acetoxyethyl)nicotinamide (SG-209)], in addition to nitroglycerin (TNG) and pinacidil (a potent K+ channel opener) under a constant perfusion flow rate to the pancreas. Nicorandil, SG-89, and TNG elicited a dose-dependent increase in pancreatic fluid secretion, showing increases in bicarbonate and amylase concentrations. In contrast, SG-209 and pinacidil did not stimulate pancreatic secretion. Furthermore, stimulatory action of nicorandil was not inhibited by treatment with an intraarterial infusion of tetraethylammonium (TEA). These results suggest that nicorandil has direct secretory properties on pancreatic exocrine glands and its nitrate moiety has an important role in the stimulation of pancreatic exocrine secretion, but increasing flow rate and K+ channel opening action do not participate in the secretion.

Amylases↗
PubMedDate not supplied

Abolition of drug-induced early afterdepolarizations by potassium channel activators in guinea-pig Purkinje fibres.

1. Drug-induced early afterdepolarizations (EAD) are considered to be the underlying mechanism of the polymorphic ventricular dysrhythmia torsades de pointes. Sotalol and disopyramide are well known to generate EAD. Therefore, it was of interest to study the effects of potassium channel activators, such as nicorandil, pinacidil and lemakalim, on those drug-induced EAD in spontaneously beating guinea-pig Purkinje fibres using the intracellular microelectrode technique. 2. Early afterdepolarizations induced by sotalol at concentrations of 80 and 160 micromol/L could be completely abolished by nicorandil at concentrations between 50 and 500 micromol/L. The extracellular K+ concentration was 2.7 mmol/L. 3. Disopyramide-induced EAD at concentrations of 10, 20 and 30 micromol/L in a Tyrode's solution containing 1.35 mmol/L K+ and these EAD were abolished by pinacidil (30 and 100 micromol/L) and lemakalim (10 and 30 micromol/L). 4. Early afterdepolarizations could be regenerated by superfusion of Purkinje fibres with K+ channel activator-free Tyrode's solution containing either sotalol or disopyramide. 5. Our results demonstrate that drug-induced EAD can be abolished by K+ channel activators and, therefore, may provide anti-arrhythmic effects in heart diseases.

Animals↗
PubMed1997

Chronotropic and inotropic effects of terikalant on isolated, blood-perfused atrial and ventricular preparations of dogs.

We investigated the effects of terikalant, which blocks inward rectifier K+ current, on the sinus rate, atrial and ventricular contractile force in the isolated, blood-perfused right atrial and left ventricular preparations of dogs, and the effects of terikalant on the negative cardiac responses to acetylcholine, adenosine or pinacidil (an ATP-sensitive K+ channel opener) and on the positive cardiac responses to norepinephrine. Terikalant (1-100 nmol) decreased sinus rate and briefly and slightly increased atrial contractile force in isolated atria. However, terikalant did not increase ventricular contractile force in isolated ventricles. Neither propranolol nor atropine inhibited the positive inotropic and negative chronotropic responses to terikalant, respectively. Terikalant (10 or 30 nmol) did not significantly affect the negative cardiac responses to acetylcholine, adenosine nor pinacidil and the positive responses to norepinephrine. These results suggest that terikalant decreases sinus rate with a small changes in myocardial contractile force and does not affect the cardiac responses to muscarinic and adenosine receptor agonists, ATP-sensitive K+ channel openers nor beta-adrenoceptor agonists in the dog heart.

Acetylcholine↗
PubMed1991

Effects of ATP-sensitive K+ channel blockers on the action potential shortening in hypoxic and ischaemic myocardium.

1. In order to determine whether activation of adenosine triphosphate (ATP)-sensitive K+ channels exclusively explains the hypoxia- and ischaemia-induced action potential shortening, effects of tolbutamide and glibenclamide on changes in action potential duration (APD) during hypoxia, metabolic blockade or experimental ischaemia were examined in guinea-pig and canine isolated myocardium by standard microelectrode techniques. 2. With use of patch clamp techniques, activity of ATP-sensitive K+ channels was recorded from open cell-attached patches of guinea-pig isolated ventricular myocytes. The probability of opening of the K+ channels was decreased by 2 mM tolbutamide and 20 microM glibenclamide to almost the same extent, whereas it was increased by 100 microM pinacidil. 3. In guinea-pig papillary muscles a marked shortening of the action potential produced by 100 microM pinacidil was completely antagonized by 2 mM tolbutamide or 20 microM glibenclamide. 4. In guinea-pig papillary muscles exposed to hypoxic, glucose-free solution or dinitrophenol (10 microM)-containing, glucose-free solution, APD declined gradually and twitch tension decreased. Pretreatment with glibenclamide partially but significantly inhibited the action potential shortening, whereas tolbutamide failed to improve it during hypoxia or metabolic blockade. 5. When in canine isolated myocardium, experimental ischaemia was produced by the cessation of coronary perfusion, APD was gradually shortened. The action potential shortening was partially but not completely inhibited by pretreatment with 20 microM glibenclamide. 6. These results suggest that changes in membrane current(s) other than the outward current through ATP-sensitive K+ channels also contribute to the action potential shortening in hypoxic or ischaemic myocardium.

Action Potentials↗
PubMed1992

Lack of effect of potassium channel openers on ATP-modulated potassium channels recorded from rat ventromedial hypothalamic neurones.

1. Single neuronal cells were freshly isolated from the ventromedial hypothalamic nuclei (VMHN) of the rat brain. Currents through ATP-modulated and large conductance (160 and 250 pS) calcium-activated potassium channels were recorded by the cell-attached and excised inside-out patch techniques. 2. BRL38227 (lemakalim; 30-90 microM) applied to the superfusing medium produced no change in firing rate of isolated glucose-receptive VMHN neurones in cell-attached recordings. 3. BRL38227, at concentrations of between 30-100 microM applied to the intracellular (cytoplasmic) aspect of inside-out patches, had no effect on the activity of ATP-sensitive K+ channels in the absence of ATP or in the presence of a sub-maximal inhibitory concentration (3 mM) of ATP. Cromakalim, pinacidil, minoxidil sulphate and diazoxide also produced no effect under these conditions. 4. The potassium channel openers (KCO's) were tested on ATP-activated potassium channels recorded from a further subpopulation of VMHN neurones. Application of BRL38227 (up to and including 100 microM) to this channel in inside-out patches either in the absence of ATP or when activated by 5 mM ATP had no effect on channel activity. Identical results were obtained with cromakalim and pinacidil. 5. BRL38227 had no effect on either of the large conductance (250 pS and 160 pS) calcium-activated potassium channels in VMHN neurones. 6. Intracellular recordings were made from glucose-receptive VMHN neurones in rat brain slices. Cromakalim (50 microM) or diazoxide (60 microM) did not alter the firing rate or passive membrane properties of these neurones demonstrated to be sensitive to tolbutamide (0.1 mM). 7. These results show that the KCO's tested in this study have no effect either on VMHN neurones contained in brain slices or on the activity of any of the ATP-modulated potassium channels under isolated patch conditions associated with these neurones.

Adenosine Triphosphate↗
PubMed1992

Mechanism of the vasodilator action of calcitonin gene-related peptide in conscious rats.

1. The aim of this study was to investigate whether the hypotensive effect of rat alpha-calcitonin gene-related peptide (alpha CGRP) in conscious rats is mediated by endothelium-derived nitric oxide (NO) or the opening of adenosine 5'-triphosphate (ATP)-sensitive potassium (KATP) channels. 2. Dose-mean arterial pressure (MAP)-response curves of alpha CGRP were examined in the presence of vehicle, phenylephrine, KATP channel antagonist glibenclamide or NO synthase inhibitors, NG-nitro-L-arginine methyl ester (L-NAME) and NG-nitro-D-arginine methyl ester (D-NAME). Dose-MAP-response curves for sodium nitroprusside were also constructed in the presence and absence of L-NAME and D-NAME. 3. alpha CGRP and nitroprusside produced dose-dependent reductions in MAP which were potentiated by phenylephrine. Both L-NAME and D-NAME attenuated the depressor response to alpha CGRP but not nitroprusside. 4. Dose-MAP-response curves for pinacidil, a KATP-channel activator, were also examined in the presence of glibenclamide or vehicle. Glibenclamide attenuated pinacidil- but not alpha CGRP-induced reductions in MAP. 5. It is concluded that the hypotensive effects of alpha CGRP are partially mediated via endothelium-derived NO but not via the opening of KATP channels.

Adenosine Triphosphate↗
PubMed1994

Modulation of vasodilatation to levcromakalim by adenosine analogues in the rabbit ear: an explanation for hypoxic augmentation.

1. We have used a rabbit isolated ear, buffered-perfused preparation to investigate the effects of adenosine analogues on the vasodilatation to the potassium channel opener, levcromakalim (the active (-)-enantiomer of cromakalim). We have examined the effects of 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), a selective adenosine A1 antagonist, on vasodilatation to levcromakalim under hypoxic conditions and also following inhibition of nitric oxide synthesis. 2. Levcromakalim relaxed preconstricted preparations with an EC50 = 369 +/- 48 nM and maximum relaxation of tone (Rmax) = 81.0 +/- 3.2%. In the presence of 1 microM N6-cyclohexyladenosine (CHA) a selective adenosine A1 agonist, there was a significant (P < 0.01) leftward shift in the concentration-response curve with an EC50 = 194 +/- 54 nM and Rmax = 93.2 +/- 2.0%. Conversely, the presence of CHA did not influence vasodilatation to either pinacidil or sodium nitroprusside. 3. Hypoxia also significantly (P < 0.001) increased the vasodilator potency of levcromakalim (EC50 = 134 +/- 22 nM), and this enhancement was completely reversed (EC50 = 380 +/- 107 nM, P < 0.01) by pretreatment of the preparations with 5 microM DPCPX, a selective A1 adenosine antagonist. However, under normoxic conditions DPCPX did not influence vasodilatation to levcromakalim. 4. Inhibition of nitric oxide synthesis with 100 microM NG-nitro-L-arginine methyl ester (L-NAME) caused a significant (P < 0.001) leftward shift in the concentration-response curve to levcromakalim (EC50 = 73.0 +/- 7.6 nM). Pretreatment of preparations with DPCPX partially reversed the increase in potency found in the absence of nitric oxide synthesis (EC50 = 153 +/- 18 nM, P < 0.001). 5. We have shown that an adenosine Al agonist may increase the potency of levcromakalim indicating that adenosine receptor activation may augment the vasodilator activity of levcromakalim. That responses to levcromakalim but not those to pinacidil were affected by CHA points to further differences in the pharmacology of these potassium channel openers. The reversal by the adenosine Al antagonist of the hypoxic-potentiation of vasodilatation to levcromakalim, and also augmentation following inhibition of nitric oxide synthesis, suggests that under these conditions there is an endogenous release of adenosine which may enhance responses to levcromakalim. The findings of this study suggest that levcromakalim may selectively dilate vessels where there is elevated adenosine release.

Adenosine↗
PubMed1996

Two types of ATP-sensitive potassium channels in rat portal vein smooth muscle cells.

1. Single-channel recordings were made from single, enzymatically isolated smooth muscle cells of rat portal vein by the patch-clamp technique. 2. Unitary potassium currents were identified through two types of K-channels with conductances in 60:130 mM K-gradient of 50 and 22 pS; these are referred to as LK and MK channels respectively. 3. The LK channels became extremely active if isolated patches were created into nucleotide-free solution; activity was inhibited by ATP applied to the inner surface of the patch with a half maximal inhibition (Ki) of 11-23 microM. Channel activity declined and disappeared with time and could be regenerated by a brief application of Mg-ATP or a nucleoside diphosphate such as UDP (in the presence of Mg). LK channel activity was rarely stimulated by levcromakalim and not by pinacidil (K-channel openers, KCOs) but was blocked by glibenclamide. 4. Activity of MK channels declined if isolated patches were created into nucleotide free solution; activity reappeared if UDP or ATP alone (in the presence of Mg) was applied; pinacidil or levcromakalim in the presence of ATP or UDP further increased channel activity which was blocked by glibenclamide. 5. The LK channel inhibited by ATPi is very similar in its conductance and other properties to the KATP channel described in tissues other than smooth muscle, in its conductance and properties the MK channel resembles the KNDP channel we have previous described as present in other smooth muscles and opening in responses to KCOs.

Adenosine Triphosphate↗
PubMed1996

Effects of tedisamil (KC-8857) on cardiac electrophysiology and ventricular fibrillation in the rabbit isolated heart.

1. The direct cardiac electrophysiological and antifibrillatory actions of tedisamil (KC-8857) were studied in rabbit isolated hearts. 2. Tedisamil (1, 3, and 10 microM), prolonged the ventricular effective refractory period (VRP) from 120 +/- 18 ms (baseline) to 155 +/- 19, 171 +/- 20, and 205 +/- 14 ms, respectively. Three groups of isolated hearts (n = 6 each) were used to test the antifibrillatory action of tedisamil. Hearts were perfused with 1.25 microM pinacidil, a KATP channel activator. Hearts were subjected to hypoxia for 12 min followed by 40 min of reoxygenation. Ventricular fibrillation (VF) developed during hypoxia and reoxygenation in both the control and 1 microM tedisamil-treated groups (5/6 and 4/6, respectively). Tedisamil (3 microM) reduced the incidence of VF (0/6, P = 0.007 vs. control). 3. In a separate group of hearts, VF was initiated by electrical stimulation. The administration of 0.3 ml of 10 mM tedisamil, via the aortic cannula, terminated VF in all hearts, converting them to normal sinus rhythm. 4. Tedisamil (3 microM) reversed pinacidil-induced negative inotropic effects in rabbit isolated atrial muscle which were equilibrated under normoxia, as well as in atrial muscle subjected to hypoxia and reoxygenation. 5. The results demonstrate a direct antifibrillatory action of tedisamil in vitro. The mechanism responsible for the observed effects may involve modulation by tedisamil of the cardiac ATP-regulated potassium channel, in addition to its antagonism of IK and Ito.

Animals↗
PubMed1991

Role of K+ channels in spontaneous electrical and mechanical activity of smooth muscle in the guinea-pig mesotubarium.

1. The spontaneous electrical and mechanical activity and the efflux rate of 86Rb+ in the guinea-pig mesotubarium were studied in the presence of agents interacting with K+ channels. 2. Tetraethylammonium (TEA, 10 mM) increased the amplitude of the action potentials while having no consistent effect on the frequency or amplitude of spontaneous contractions. 3. 4-Aminopyridine (4-AP, 1-5 mM) caused a graded increase in the duration of the contractions and of the electrical slow waves, and a decrease in the duration of the relaxed period between contractions. At 4 mM-4-AP or more the cell was unable to repolarize from the slow wave and the membrane depolarized to -26 mV from the normal resting potential of -63 mV. The rate of 86Rb+ efflux in the presence of 5 mM-4-AP was higher than that at 60 mM-K+, where the membrane potential is -24 mV. 4. 4-AP (5 mM) evoked a contracture in Ca(2+)-free solution, containing 1 mM-EGTA, both at the normal [K+]o of 5.9 mM and at 60 mM-K+, suggesting release of intracellular Ca2+. 5. Apamin (0.1-1 microM) and charybdotoxin (1-10 nM), blockers of Ca(2+)-dependent K+ channels, were without effects on the spontaneous electrical and mechanical activity. 6. The K+ channel opener pinacidil (10 microM) inhibited the spontaneous contractions and hyperpolarized the membrane by about 7 mV. The permeability to 86Rb+ was increased by a factor of 1.4. 7. It is concluded that different K+ channels are involved in the generation of spikes and slow waves: one sensitive to TEA and responsible for repolarization of the individual action potential, and another sensitive to 4-AP and responsible for repolarization of the slow wave. The duration of the relaxed period can be influenced by activation of K+ channels sensitive to pinacidil.

4-Aminopyridine↗
PubMed2004

Pharmacological modulation of the ATP sensitive potassium channels during repeated coronary occlusions: no effect on myocardial ischaemia or function.

BACKGROUND: Repeated episodes of myocardial ischaemia may lead to ischaemic preconditioning. This is believed to be mediated by the ATP sensitive potassium channels. OBJECTIVE: To examine the effect of pharmacological modulation of the ATP sensitive potassium channels during repeated coronary occlusions. DESIGN: Double blind, double dummy study. METHODS: 38 patients with a proximal stenosis of the left anterior descending coronary artery and no visible coronary collateral vessels underwent three identical 90 second balloon occlusions, each followed by five minutes of reperfusion. The patients were randomised to pinacidil 25 mg, glibenclamide 10.5 mg, or matching placebo 90 minutes before the start of the procedure. Myocardial ischaemia was measured by continuous monitoring of ECG ST segment changes. Changes in left ventricular function were recorded with a miniature radionuclide detector, and angina was scored on the Borg scale. RESULTS: In all patients the first balloon occlusion led to significant ST segment elevation, a clear decrease in left ventricular ejection fraction, and angina pectoris. This response was not attenuated at the second or third balloon occlusion, either in the placebo group or in the patients pretreated with pinacidil or glibenclamide. CONCLUSIONS: Under the given experimental conditions, this randomised and double blind study did not support the view that the human myocardium has an intrinsic protective mechanism that is activated by short lasting episodes of ischaemia.

Adenosine Triphosphate↗
PubMed2002

ATP-sensitive K(+) channels composed of Kir6.1 and SUR2B subunits in guinea pig gastric myocytes.

This study was designed to identify the single-channel properties and molecular entity of ATP-sensitive K(+) (K(ATP)) channels in guinea pig gastric myocytes with patch-clamp recording and RT-PCR. Pinacidil and diazoxide activated K(ATP) currents in a glibenclamide-sensitive manner. The open probability of channels was enhanced by the application of 10 microM pinacidil from 0.085 +/- 0.04 to 0.20 +/- 0.05 (n = 7) and was completely blocked by 10 microM glibenclamide. Single-channel conductance was 37.3 +/- 2.5 pS (n = 4) between -80 and -20 mV in symmetrical K(+) gradient conditions. In inside-out mode, K(ATP) channels showed no spontaneous openings and were activated by the application of nucleotide diphosphates to the cytoplasmic side. These single-channel properties are similar to those of the nucleotide diphosphate-dependent K(+) channels in vascular smooth muscle, which are composed of Kir6.1 and sulfonylurea receptor (SUR)2B. RT-PCR demonstrated the presence of Kir6.1, Kir6.2, and SUR2B in guinea pig stomach smooth muscle cells. These results suggest that K(ATP) channels in smooth muscle cells of the guinea pig stomach are composed of Kir6.1 and SUR2B.

ATP-Binding Cassette Transporters↗
PubMed1994

Evidence against KATP channel involvement in adenosine receptor-mediated dilation of epicardial vessels.

The purpose of this study was to determine whether ATP-glyburide-sensitive K+ (KATP-glyburide) channels are involved in the adenosine-induced vasorelaxation of porcine and canine epicardial vessels in vitro. Adenosine and its analogues, 2-chloroadenosine (CAD), 5'-N-ethylcarboxamidoadenosine (NECA), R-N6-(2-phenylisopropyl)adenosine (R-PIA), N6-cyclopentyladenosine (CPA), N6-[2-(3,5-dimethoxyphenyl)-2-(2-methylphenyl)]adenosine (DPMA), 2-phenylaminoadenosine (CV-1808), 2-[m-(carboxyethyl)phenylamino]-5'-N-ethylcarboxamidoadenosine (CGS-22988), 2-[(2-cyclohexylethyl)amino]adenosine (CGS-22492), 2-[(p-amino)phenethylamino]adenosine (APE), and 2-(1-octynyl)adenosine (YT-146) (10 nM-100 microM), produced concentration-dependent relaxations in endothelium-intact and -denuded arterial ring segments contracted with 30 mM KCl, 10 nM endothelin-1, or 10 microM prostaglandin F2 alpha. Sodium nitroprusside (SNP; 1 nM-10 microM) and KATP-channel activator, pinacidil (10 nM-10 microM), also produced similar vasodilatory responses. Glyburide, a KATP-channel blocker, caused a rightward shift of the concentration-response curve to pinacidil but did not alter the responses elicited by SNP or adenosine and its analogues. The data suggest that KATP-glyburide channels are not involved in the mechanism whereby adenosine and its analogues elicit their vasorelaxant response in isolated porcine or canine epicardial vessels.

Adenosine Triphosphate↗