Disposition of L-carnitine and its short-chain esters, acetyl-L-carnitine and propionyl-L-carnitine, in the rat isolated perfused liver.
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Acetylcarnitine↗
Biomedical subjects
A M Evans
Publications and source records attributed to A M Evans.
ET(A) receptors are the primary mediators of myofilament calcium sensitization induced by ET-1 in rat pulmonary artery smooth muscle: a tyrosine kinase independent pathway.
We have investigated the possibility that ET-1 can induce an increase in myofilament calcium sensitivity in pulmonary artery smooth muscle. Arterial rings were permeabilized using alpha-toxin (120 microg ml(-1)), in the presence of A23187 (10 microM) to 'knock out' Ca2+ stores, and pre-constricted with pCa 6.8 (buffered with 10 mM EGTA). In the presence of this fixed Ca2+ concentration, 1 microM ET-1 induced a sustained, reversible constriction of 0.15 mN. Pulmonary arterial rings were freeze-clamped at the peak of the induced constriction (time matched). Subsequent densitometric analysis revealed that ET-1 (1 microM) increased the level of phosphorylated myosin light chains by 34% compared to an 11% increase in the presence of pCa 6.8 alone. In contrast to ET-1, the selective ET(B) receptor agonist Sarafotoxin S6C (100 nM) failed to induce a significant constriction. The constriction induced by 1 microM ET-1 was reversibly inhibited when the preparation was preincubated (15 min) with the ETA receptor antagonist BQ 123 (100 microM). The constriction measured 0.13 mN in the absence and 0.07 mN in the presence of 100 microM BQ 123. In contrast, the constriction induced by 1 microM ET-1 measured 0.19 mN in the absence and 0.175 mN following a 15 min pre-incubation with the ET(B) antagonist BQ 788 (100 microM). The constriction induced by 1 microM ET-1 measured 0.14 mN in the presence and 0.13 mN following pre-incubation with the tyrosine kinase inhibitor Tyrphostin A23 (100 microM). We conclude that ET-1 induced an increase in myofilament calcium sensitivity in rat pulmonary arteries via the activation of ET(A) receptors and by a mechanism(s) independent of tyrosine kinase.
Actin Cytoskeleton↗
Application of a loading wash-out method for investigating the hepatocellular efflux of a hepatically-generated metabolite, morphine-3-glucuronide.
Previous studies using the rat isolated perfused liver demonstrated that the hepatic disposition of morphine-3-glucuronide is membrane permeability-rate limited, and that the movement of the metabolite across hepatic sinusoidal and canalicular membranes is partly via carrier-mediated transport systems. As a consequence of the membrane permeability-limitation, the biliary excretion of hepatically-generated morphine-3-glucuronide is much more efficient than that of morphine-3-glucuronide reaching the liver via the vasculature. We have quantitated the cellular efflux kinetics (cell-to-blood and cell-to-bile) of morphine-3-glucuronide in the rat isolated perfused liver using a loading wash-out design. In the 'loading' phase, morphine was infused into the liver (2.7 microM) and the biliary excretion and sinusoidal efflux of morphine-3-glucuronide was assessed under steady-state conditions. Subsequently, the infusion was stopped and the concentration vs time profile of morphine-3-glucuronide in outflow perfusate (the wash-out phase) was determined. A physiologically-based pharmacokinetic model was used to determine the rate-constants for the movement of hepatically-generated morphine-3-glucuronide into the sinusoidal and canalicular spaces of the liver, and the associated membrane permeability terms. The mean (+/-s.d.) rate constants for the biliary excretion and sinusoidal efflux of morphine-3-glucuronide were determined to be 0.160 +/- 0.043 and 0.169 +/- 0.068 min(-1), respectively, and the corresponding membrane permeability parameters were 1.12 and 1.18 mL min(-1), respectively. The sinusoidal membrane permeability term was significantly less than hepatic blood flow in the rat. The volume of distribution of hepatically-generated morphine-3-glucuronide (207.5 +/- 74.8 mL) was found to be approximately 50-times the intracellular space of the rat liver, suggesting that hepatically-generated morphine-3-glucuronide accumulates within hepatocytes. The results indicate that hepatically-generated morphine-3-glucuronide undergoes intracellular accumulation, probably as a consequence of poor membrane permeability.
Algorithms↗
Relaxation of endothelin-1-induced pulmonary arterial constriction by niflumic acid and NPPB: mechanism(s) independent of chloride channel block.
We investigated the effects of the Cl- channel blockers niflumic acid, 5-nitro-2-(3-phenylpropylamino)-benzoic acid (NPPB) and 4, 4'-diisothiocyanatostilbene-2,2'-disulphonic acid (DIDS) on endothelin-1 (ET-1)-induced constriction of rat small pulmonary arteries (diameter 100-400 microm) in vitro, following endothelium removal. ET-1 (30 nM) induced a sustained constriction of rat pulmonary arteries in physiological salt solution. Arteries preconstricted with ET-1 were relaxed by niflumic acid (IC50: 35.8 microM) and NPPB (IC50: 21.1 microM) in a reversible and concentration-dependent manner. However, at concentrations known to block Ca++-activated Cl- channels, DIDS (</=500 microM) had no effect on the ET-1-induced constriction. Similar results were obtained when pulmonary arteries were preincubated with these Cl- channel blockers. When L-type Ca++ channels were blocked by nifedipine (10 microM), the ET-1-induced (30 nM) constriction was inhibited by only 5.8%. However, niflumic acid (30 microM) and NPPB (30 microM) inhibited the ET-1-induced constriction by approximately 53% and approximately 60%, respectively, both in the continued presence of nifedipine and in Ca++-free physiological salt solution. The Ca++ ionophore A23187 (10 microM) also evoked a sustained constriction of pulmonary arteries. Surprisingly, the A23187-induced constriction was also inhibited in a reversible and concentration-dependent manner by niflumic acid (IC50: 18.0 microM) and NPPB (IC50: 8.8 microM), but not by DIDS (</= 500 microM). Our data suggest that the primary mechanism by which niflumic acid and NPPB inhibit pulmonary artery constriction is independent of Cl- channel blockade. One possibility is that these compounds may block the Ca++-dependent contractile processes.
4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
Hepatic disposition of the acyl glucuronide1-O-gemfibrozil-beta-D-glucuronide: effects of dibromosulfophthalein on membrane transport and aglycone formation.
The liver plays an important role in the disposition of acyl glucuronides by determining their extent of formation, biliary excretion, and efflux into blood. Thus, both intrahepatic and extrahepatic exposure to these reactive polar conjugates depends on the efficiency of hepatic transport mechanisms, which may be shared with other nonbile acid organic anions. Using the isolated perfused rat liver preparation, the hepatic disposition of the acyl glucuronide, 1-O-gemfibrozil-beta-D-glucuronide, was examined in the presence of the organic anion dibromosulfophthalein (DBSP). Using a recirculating system, livers were perfused for 90 min with an erythrocyte-free perfusion medium containing 1% (w/v) albumin and 1-O-gemfibrozil-beta-D-glucuronide (3 microM) alone (n = 6) or with DBSP (200 microM, n = 7). The glucuronide was avidly taken up by the liver, excreted into bile, and hydrolyzed within the liver to its aglycone, gemfibrozil. DBSP significantly (P <.05) lowered the conjugate's mean hepatic clearance (8.98-5.17 ml/min), intrinsic clearance (44.0-17.7 ml/min), and fraction eliminated in bile (72. 8-48.7% of the dose), while increasing perfusate gemfibrozil concentrations (0.52-0.92 microM at 90 min). Furthermore, DBSP significantly (P <.05) lowered the ratio of intrahepatic to unbound perfusate concentrations of 1-O-gemfibrozil-beta-D-glucuronide (139. 0-35.0) and showed a trend to lower the ratio of bile to intrahepatic concentrations (111.3-76.2, P =.05). Thus, the study demonstrated that DBSP inhibited both the sinusoidal uptake and canalicular transport of 1-O-gemfibrozil-beta-D-glucuronide, suggesting that the hepatic membrane transport of acyl glucuronides is carrier mediated and shared with other organic anions.
Animals↗
Effect of cationic drugs on the renal secretion of ranitidine in the rat isolated perfused kidney.
1. The rat isolated perfused kidney (IPK) was used to determine whether the renal tubular secretion of ranitidine is influenced by clinically relevant concentrations of other organic cationic drugs (amantadine, pseudoephedrine, triamterene and trimethoprim) that also undergo tubular secretion. 2. Ranitidine and [3H]-ranitidine were administered to the recirculating perfusion medium as a loading dose followed by a constant infusion to maintain clinically relevant perfusate ranitidine concentrations in the range 400-700 ng/mL. The renal clearance of ranitidine (CL[R]) was calculated, as was glomerular filtration rate (GFR), from the renal clearance of [14C]-inulin. 3. A total of 20 perfusions were performed and, in each case, ranitidine was administered for 80 min. In four control IPK, no drug other than ranitidine was administered. In the remaining IPK, amantadine, pseudoephedrine, triamterene or trimethoprim (n = 4 in each case) were administered to achieve low, medium and high concentrations during the 20-40, 40-60 and 60-80 min periods, respectively. 4. The mean (+/- SD) unbound fraction of ranitidine in the perfusion medium was 0.889 +/- 0.046 and was not altered (P>0.05) by the presence of the other drugs. 5. The CL(R)/GFR ratio for ranitidine in all kidneys was substantially greater than unity and had a mean value of 10.65 or greater in control kidneys, indicating extensive net tubular secretion. 6. The CL(R)/GFR was not affected (P>0.05) by amantadine, pseudoephedrine or triamterene at any concentration or by trimethoprim at the low concentration. However, medium (2000 ng/mL) and high (5000 ng/mL) concentrations of trimethoprim caused significant reductions in CL(R)/GFR of 20 and 28%, respectively (P<0.05). 7. The results indicate that at clinically relevant concentrations the renal tubular secretion of ranitidine is inhibited by trimethoprim, but not by amantadine, pseudoephedrine or triamterene.
Amantadine↗
Differential effects of hypoxia on the intracellular Ca2+ concentration of myocytes isolated from different regions of the rat pulmonary arterial tree.
Hypoxic pulmonary vasoconstriction (HPV) may be mediated, in part, by an oxygen-sensing mechanism intrinsic to pulmonary arterial smooth muscle. It has been proposed that hypoxia inhibits a K+ conductance, which promotes membrane depolarization, subsequent activation of L-type Ca2+ channels and ultimately constriction. We have monitored hypoxia-induced changes in the intracellular Ca2+ concentration ([Ca2+]i) of single myocytes isolated from the rat pulmonary arterial tree using microspectrofluorimetry and ratiometric measurement of indo-1 fluorescence. The basal level of [Ca2+]i was in the range 35-80 nM and cells were quiescent at rest exhibiting no spontaneous oscillations in [Ca2+]i. When the extracellular K+ concentration ([K+]o) was raised to 20 mM, the [Ca2+]i increased from approximately 60 to approximately 100 nM. This increase was abolished by nifedipine, demonstrating the presence, and need for activation, of functional voltage-gated L-type Ca2+ channels. Hypoxia (PO2 < or = 30 mmHg; throughout) had little effect on the resting [Ca2+]i in myocytes isolated from either the main intrapulmonary artery, or its primary, secondary or tertiary branches. However, upon raising the [Ca2+]i by increasing [K+]o to 20 mM, hypoxia was found to lower [Ca2+]i from approximately 110 to approximately 70 nM, in cells isolated from the main conduit and primary branches of the intrapulmonary artery. In marked contrast, when [Ca2+]i was raised, by increasing [K+]o to 20 mM, in myocytes isolated from secondary and tertiary branches of the intrapulmonary artery, hypoxia induced a further reversible increase in the [Ca2+]i from approximately 160 to approximately 240 nM. Neither hypoxia alone nor in combination with 20 mM K(+)o induced any increase in the [Ca2+]i in the presence of nifedipine. We conclude that hypoxia may modulate [Ca2+]i in rat pulmonary artery myocytes only following its elevation by a depolarizing stimulus.
Animals↗
Resting potentials and potassium currents during development of pulmonary artery smooth muscle cells.
The pulmonary circulation changes rapidly at birth to adapt to extrauterine life. The neonate is at high risk of developing pulmonary hypertension, a common cause being perinatal hypoxia. Smooth muscle K+ channels have been implicated in hypoxic pulmonary vasoconstriction in adults and O2-induced vasodilation in the fetus, channel inhibition being thought to promote Ca2+ influx and contraction. We investigated the K+ currents and membrane potentials of pulmonary artery myocytes during development, in normal pigs and pigs exposed for 3 days to hypoxia, either from birth or from 3 days after birth. The main finding is that cells were depolarized at birth and hyperpolarized to the adult level of -40 mV within 3 days. Hypoxia prevented the hyperpolarization when present from birth and reversed it when present from the third postnatal day. The mechanism of hyperpolarization is unclear but may involve a noninactivating, voltage-gated K+ channel. It is not caused by increased Ca2+-activated or delayed rectifier current. These currents were small at birth compared with adults, declined further over the next 2 wk, and were suppressed by exposure to hypoxia from birth. Hyperpolarization could contribute to the fall in pulmonary vascular resistance at birth, whereas the low K+-current density, by enhancing membrane excitability, would contribute to the hyperreactivity of neonatal vessels. Hypoxia may hinder pulmonary artery adaptation by preventing hyperpolarization and suppressing K+ current.
Aging↗
The role of L-type Ca2+ current and Na+ current-stimulated Na/Ca exchange in triggering SR calcium release in guinea-pig cardiac ventricular myocytes.
OBJECTIVE: This study examines the relative ability of sodium current (INa)-stimulated reverse mode Na/Ca exchange and the L-type calcium current (ICa) to trigger calcium-induced calcium release (CICR) in guinea-pig ventricular myocytes. METHODS: Cytosolic Ca2+ transients were recorded from enzymatically dissociated guinea-pig ventricular myocytes using Indo-1. Macroscopic membrane currents were simultaneously recorded using the whole-cell patch-clamp technique. RESULTS: At room temperature (22-25 degrees C) Ca2+ transients were associated with the activation of INa, ICa or INa plus ICa in combination. However, after ICa was blocked by verapamil (10 microM), no Ca2+ transient could be evoked by the activation of INa alone at either -40 or +5 mV. Similar results were obtained with 5 and 8 mM intracellular sodium, and when the temperature of the bathing solution was raised to 35 degrees C and cAMP (10 microM) added to the pipette solution. CONCLUSIONS: From consideration of the relative magnitudes of the Ca2+ influx via ICa and Na/Ca exchange and thermodynamic considerations, we suggest that ICa is the major source of 'trigger' calcium for CICR (and cardiac contraction) under normal conditions. Although the Na/Ca exchanger was incapable of triggering CICR under the conditions of these experiments, we suggest that it may become more important when cytosolic Ca2+ is elevated, a condition which will also lead to decrease the amplitude of ICa.
Animals↗
Comparison of the disposition of hepatically-generated morphine-3-glucuronide and morphine-6-glucuronide in isolated perfused liver from the guinea pig.
PURPOSE: Humans and guinea pigs metabolise morphine extensively, forming the isomers morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) in relatively similar ratios. Both metabolites are formed in the liver, and their greater polarity relative to the parent aglycone may limit their permeability across hepatic membranes. This study compared the disposition of hepatically-generated M3G and M6G in perfused livers isolated from guinea pigs. METHODS: Livers were perfused at 30 ml/min in a non-recirculating manner with Krebs bicarbonate buffer containing morphine (6 to 7 microM). Perfusing medium, venous perfusate and bile were collected at regular intervals and concentrations of morphine, M3G and M6G determined by reversed-phase HPLC. RESULTS: Concentrations of morphine, M3G and M6G in perfusate and the rates of biliary excretion of M3G and M6G were consistent between 20 and 50 min of perfusion. The mean (+/-s.d.) ratio for the rate of formation of M3G relative to M6G was 3.7 +/- 1.5. A mean 33 +/- 3% of morphine extracted by the liver was recovered as summed M3G and M6G. Of the M3G and M6G formed during a single passage, 19 +/- 11% and 9 +/- 9%, respectively, was excreted into bile; the values were significantly different (P = 0.002). CONCLUSIONS: A greater fraction of hepatically-generated M3G excreted into bile compared to that for M6G reflects differences in their relative transport across sinusoidal and canalicular membranes of hepatocytes, possibly via carrier-mediated systems.
Analgesics, Opioid↗
Regulation of the resting potential of rabbit pulmonary artery myocytes by a low threshold, O2-sensing potassium current.
1. The contributions of specific K+ currents to the resting membrane potential of rabbit isolated, pulmonary artery myocytes, and their modulation by hypoxia, were investigated by use of the whole-cell, patch-clamp technique. 2. In the presence of 10 microM glibenclamide the resting potential (-50 +/- 4 mV, n = 18) was unaffected by 10 microM tetraethylammonium ions, 200 nM charybdotoxin, 200 nM iberiotoxin, 100 microM ouabain or 100 microM digitoxin. The negative potential was therefore maintained without ATP-sensitive (KATP) or large conductance Ca(2+)-sensitive (BKCa) K channels, and without the Na(+)-K+ ATPase. 3. The resting potential, the delayed rectifier current (IK(V)) and the A-like K+ current (IK(A)) were all reduced in a concentration-dependent manner by 4-aminopyridine (4-AP) and by quinine. 4. 4-AP was equally potent at reducing the resting potential and IK(V), 10 mM causing depolarization from -44 mV to -22 mV with accompanying inhibition of IK(V) by 56% and IK(A) by 79%. In marked contrast, the effects of quinine on resting potential were poorly correlated with its effects on both IK(A) and IK(V). At 10 mM, quinine reduced IK(V) and IK(A) by 47% and 38%, respectively, with no change in the resting potential. At 100 microM, both currents were almost abolished while the resting potential was reduced < 50%. Raising the concentration to 1 mM had little further effect on IK(A) or IK(V), but essentially abolished the resting potential. 5. Reduction of the resting potential by quinine was correlated with inhibition of a voltage-gated, low threshold, non-inactivating K+ current, IK(N). Thus, 100 microM quinine reduced both IK(N) and the resting potential by around 50%. 6. The resting membrane potential was the same whether measured after clamping the cell at -80 mV, or immediately after a prolonged period of depolarization at 0 mV, which inactivated IK(A) and IK(V), but not IK(N). 7. When exposed to a hypoxic solution, the O2 tension near the cell fell from 125 +/- 6 to 14 +/- 2 mmHg (n = 20), resulting in a slow depolarization of the myocyte membrane to -35 +/- 3 mV (n = 16). The depolarization occurred without a change in the amplitude of IK(V) or IK(A), but it was accompanied by 60% inhibition of IK(N) at 0 mV. 8. Our findings suggest that the resting potential of rabbit pulmonary artery myocytes depends on IK(N), and that inhibition of IK(N) may mediate the depolarization induced by hypoxia.
Animals↗
Effects of albumin on the disposition of morphine and morphine-3-glucuronide in the rat isolated perfused liver.
1. The effect of albumin on the disposition of morphine and hepatically generated morphine-3-glucuronide (M3G) was investigated in the single-pass rat isolated perfused liver. 2. Using a balanced cross-over design, each of 10 livers was perfused at 30 mL/min with medium containing 2.7 mumol/L morphine in the presence and absence of 10 g/L bovine serum albumin (BSA). 3. Both bile flow rate and hepatic oxygen consumption were significantly higher (P < 0.005) when BSA was present in the perfusion medium, suggestive of a change in the functional performance of the perfused liver. 4. The binding of morphine and M3G was negligible in both BSA-free and -containing perfusate. 5. Outflow perfusate contained both morphine and M3G, while the metabolite but not morphine was found in bile. The recovery of the administered morphine was approximately 100% and was not altered (P > 0.05) by the presence or absence of BSA. 6. The fraction of morphine escaping heptic extraction in the absence of BSA (mean +/- SD; 0.41 +/- 0.14) was not altered significantly (P > 0.05) by the presence of the protein in perfusate (0.35 +/- 0.13), indicating no change in the intrinsic clearance or morphine despite the difference in oxygen consumption. 7. The fraction of hepatically generated M3G excreted in bile was significantly higher (P < 0.005) when BSA was present in the perfusate than when it was not (0.44 +/- 0.14 vs 0.38 +/- 0.16, respectively). 8. The results are consistent with the concept that BSA modifies the ability of solutes, including M3G, to move through the paracellular pathway from the canalicular to the vascular space. 9. It is concluded that because albumin may modify not only the unbound fraction of a ligand in perfusate, but also the functional performance of the liver, care is needed in the interpretation of studies examining the influence of the protein on the hepatic disposition of drugs and their metabolites.
Animals↗
Excretion and metabolism of propionyl-L-carnitine in the isolated perfused rat kidney.
Propionyl-L-carnitine (PLC) is an ester of L-carnitine (LC) under evaluation for the treatment of cardiovascular disorders. The renal disposition of PLC was studied in the isolated perfused rat kidney with deuterium-labeled derivative (PLC-CD3). Kidneys of male Sprague-Dawley rats were perfused at initial PLC-CD3 concentrations of 10 (n = 4) and 200 microM (n = 5). High-performance liquid chromatography/mass spectrometry was used to quantify PLC-CD3, deuterated L-carnitine (LC-CD3) and acetyl-L-carnitine (ALC-CD3) in perfusate and urine. PLC-CD3 in perfusate decreased in a monoexponential manner with a half-life of 90 +/- 24 min (S.D.) (10 microM) and 94 +/- 11 min (200 microM). The renal excretory clearance of PLC-CD3 was significantly lower (P < .05, unpaired t test) at an initial concentration of 10 microM (45 +/- 23 microl/min) than at 200 microM (85 +/- 28 microl/min), but in both cases it was substantially less than the glomerular filtration rate, which indicates extensive tubular reabsorption. The renal excretory clearance of PLC-CD3 represented less than 6% of the total clearance, which suggests that metabolism is the major renal elimination route for this compound. The appearance in perfusate and urine of LC-CD3 and ALC-CD3 provided additional evidence for a metabolic role of the kidney. The apparent renal excretory clearance values for these metabolites were always significantly higher than the values obtained for the corresponding endogenous compounds, which suggests that LC-CD3 and ALC-CD3, as formed metabolites, underwent passive or carrier-mediated movement directly into urine.
Animals↗
Disposition of morphine in the rat isolated perfused kidney: concentration ranging studies.
The rat isolated perfused kidney was used to investigate the linearity of the renal disposition of morphine and its potential oxidative and glucuronidative metabolism by the kidney. In a set of single-dose experiments, morphine was administered to recirculating perfusion medium to achieve initial concentrations of 0.2, 2 and 20 microM (n = 4 at each concentration). In a set of multiple-dose experiments, morphine was administered to perfusate as sequential bolus doses to achieve concentrations of 0.2, 2, 20 and 200 microM (n = 6). HPLC was used to determine the concentration of morphine in perfusate and urine. Normorphine, morphine-3-glucuronide and morphine-6-glucuronide could not be detected in perfusate or urine, a result that suggests an absence of oxidative and glucuronidative metabolism of morphine by the rat kidney. The volume of distribution of morphine within the kidney was high (31 +/- 3 ml/g at 0.2 microM), which indicates extensive accumulation, and remained constant with increasing perfusate concentration. The ratio of unbound renal excretory clearance to glomerular filtration rate was always greater than unity for all kidneys, which indicates that the renal excretion of morphine involves net tubular secretion. This ratio was constant (P > .05) over the 100-fold concentration range of the single-dose study. In the multiple-dose study, the ratio was marginally but significantly (P < .05) higher at concentrations of 2, 20 and 200 microM than at 0.2 microM, a difference that cannot be explained by saturation of tubular secretion. The results suggest that the tubular secretion of morphine is not saturated over a wide range of concentrations (0.2-200 microM).
Analgesics, Opioid↗
Properties of a novel K+ current that is active at resting potential in rabbit pulmonary artery smooth muscle cells.
1. An outward current (IK(N)) was identified in rabbit pulmonary artery myocytes, which persisted after Ca(2+)-activated and ATP-sensitive K+ currents were blocked by TEA (10 mM) and glibenclamide (10 microM), respectively, and after A-like (IK(A)) and delayed rectifer (IK(V)) K+ currents were inactivated by clamping the cell at 0 mV for 10 min. It was found in smooth muscle cells at all levels of the pulmonary arterial tree. 2. The relationship between the reversal potential of IK(N) and the extracellular K+ concentration ([K+]o) was close to that expected for a K(+)-selective channel. Deviation from Nernstian behaviour at low [K+)o could be accounted for by the presence of an accompanying leakage current. 3. IK(N) is voltage gated. It has a low threshold for activation, between -80 and -65 mV, and activates slowly without delay. Activation follows an exponential time course with a time constant of 1.6 s at -60 mV. Deactivation is an order of magnitude faster than activation, with a time constant of 107 ms at -60 mV. 4. IK(N) showed a similar sensitivity to 4-aminopyridine as IK(A) and IK(V), with 49% inhibition at 10 mM. The current was not blocked by microM quinine, which did inhibit IK(A) and IK(V), by 51 and 47%, respectively. 5. Activation of IK(N) was detected at potentials close to the resting membrane potential of pulmonary artery smooth muscle cells, under physiological conditions. Thus it is likely to contribute to the resting membrane potential of these cells.
4-Aminopyridine↗
The roles of the sodium and calcium current in triggering calcium release from the sarcoplasmic reticulum.
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Animals↗
Chirality and the actions of anti-inflammatory drugs.
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Anti-Inflammatory Agents, Non-Steroidal↗
Analysis by gas chromatography-mass spectrometry of the fatty acid composition during temperature adaptation in Aphanizomenon flos-aquae, a diazotrophic cyanobacterium from the Baltic Sea.
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Adaptation, Physiological↗