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C Brugnara

Publications and source records attributed to C Brugnara.

At least 55 records · Page 3Linked to original sources
PubMed1998

Activated protein C concentrate for the treatment of meningococcal endotoxin shock in rabbits.

To evaluate the effects of activated protein C therapy in a rabbit model of meningococcal endotoxin-induced shock, we performed a prospective, blinded, placebo-controlled animal trial. Forty New Zealand White rabbits were challenged with intravenous meningococcal endotoxin (lipooligosaccharide) 100 microg/kg. Ten minutes before endotoxin challenge, animals were administered either activated protein C 1600 microg/mL (n = 20) or an equal volume of saline (n = 20) as an initial bolus. After endotoxin challenge, activated protein C treated animals were administered a continuous infusion of activated protein C 160 microg/kg/h and saline-treated animals were administered an equal volume infusion of saline. Both activated protein C treated and saline control animals demonstrated evidence of shock after endotoxin challenge; mean arterial pressure and serum bicarbonate significantly (p < .01) declined, and heart rate significantly (p < .01) increased from baseline. In activated protein C treated animals, mean plasma activated protein C activity was 5.69 microg/mL (+/- 3.2) 1 h after challenge, whereas plasma protein C activity was not detected in controls. Mean prothrombin and activated partial thromboplastin times were significantly (p < or = .01) prolonged compared with saline-treated controls. Other hematologic and chemical measurements did not differ between groups. Fifteen of 20 (75%) animals treated with activated protein C concentrate survived to 24 h, while 9 of 20 (45%) control animals survived to 24 h (p = .05). Those animals treated with activated protein C had improved survival, which corroborates the findings of early clinical studies in which replacement of protein C improved outcome.

Animals↗
PubMed1998

The effect of dietary magnesium supplementation on the cellular abnormalities of erythrocytes in patients with beta thalassemia intermedia.

BACKGROUND AND OBJECTIVE: Reduced serum or erythrocyte Mg have been reported in human beta thalassemia. These deficiencies may play a role in the cellular abnormalities characteristic of this disorder. We have therefore studied the effect of dietary Mg supplementation in patients with beta thalassemia intermedia in order to establish whether it improves the abnormalities of thalassemic erythrocytes. DESIGN AND METHODS: Plasma and erythrocyte Mg were determined in 11 patients with b thalassemia intermedia, not requiring chronic transfusion therapy, and in 17 normal controls. Inclusion criteria included normal renal and liver function and performance status of 70% or greater. Seven patients were enrolled for the Mg supplementation study, after the appropriate informed consent was obtained. They were given a starting dose of 0.6 mEq/kg/day of magnesium pidolate, divided into two oral daily doses, for four weeks. In a 70-kg subject, a daily Mg dose of 42 mEq corresponds to 504 mg of Mg, with the daily Mg intake of normal subjects being 418 +/- 120 mg for males and 343 +/- 94 mg for females. After 28 days of treatment, five of the patients continued the protocol with a daily dosage increased to 1.2 mEq magnesium pidolate/kg/day, divided into two oral administrations, for an additional four weeks. RESULTS: In patients with untransfused beta thalassemia intermedia we found reduced erythrocyte Mg (in mmol/kg Hb, 6.12 +/- 1.5, n = 11 vs. 8.69 +/- 0.89, n = 17, respectively, p < 0.0001) and normal serum Mg. In the seven patients given oral Mg supplements, at Mg dosages of 0.6 mEq/kg/day we observed significant increases in erythrocyte Mg, and significant improvement in some of the characteristic abnormalities of beta that erythrocytes (increased Na-K pump, KCl cotransport, cell dehydration, increased osmotic resistance). These changes were maintained in the 5 patients who were treated with 1.2 mEq of Mg/kg/day. Follow-up studies showed a return to baseline conditions. There were no signs of Mg toxicity, with the only side effect being diarrhea, which was generally mild, but led to discontinuation for one patient after the first four weeks. INTERPRETATION AND CONCLUSIONS: These data indicate that dietary Mg supplementation improves some of the characteristic cellular function abnormalities of b thalassemia intermedia. The possible therapeutic value of this strategy should be further tested in these patients.

Biological Transport, Active↗
PubMed1997

The antifungal antibiotic, clotrimazole, inhibits chloride secretion by human intestinal T84 cells via blockade of distinct basolateral K+ conductances. Demonstration of efficacy in intact rabbit colon and in an in vivo mouse model of cholera.

The antifungal antibiotic clotrimazole (CLT) blocks directly and with high potency the Ca2+-activated K+ channels of human erythrocytes, erythroleukemia cells, and ferret vascular smooth muscle cells. We recently reported that CLT inhibits Cl- secretion in human intestinal T84 cells, likely by affecting K+ transport (Rufo, P.A., L. Jiang, S.J. Moe, C. Brugnara, S.L. Alper, and W.I. Lencer. 1996. J. Clin. Invest. 98:2066-2075). To determine if CLT had direct effects on K+ conductances in T84 cells, we selectively permeabilized apical membranes of confluent T84 cell monolayers using the ionophore amphotericin B. This technique permits direct measurement of basolateral K+ transport. We found that CLT and a stable des-imidazolyl derivative inhibited directly two pharmacologically distinct basolateral membrane K+conductances, but had no effect on apical membrane Cl- conductances. The effects of CLT on Cl- secretion were also examined in intact tissue. CLT inhibited forskolin-induced Cl- secretion in rabbit colonic mucosal sheets mounted in Ussing chambers by 91%. CLT also inhibited cholera toxin-induced intestinal Cl- secretion in intact mice by 94%. These data provide direct evidence that CLT blocks Cl- secretion in intestinal T84 cells by inhibition of basolateral K+ conductances, and show that CLT inhibits salt and water secretion from intact tissue in vitro and in vivo. The results further support the suggestion that CLT and its metabolites may show clinical efficacy in the treatment of secretory diarrheas of diverse etiologies.

Animals↗
PubMed1997

Oral magnesium supplements reduce erythrocyte dehydration in patients with sickle cell disease.

Intracellular polymerization and sickling depend markedly on the cellular concentration of sickle hemoglobin (Hb S). A possible therapeutic strategy for sickle cell disease is based on reducing the cellular concentration of Hb S through prevention of erythrocyte dehydration. The K-Cl cotransporter is a major determinant of sickle cell dehydration and is inhibited by increasing erythrocyte Mg content. We studied 10 patients with sickle cell disease before treatment and after 2 and 4 wk of treatment with oral Mg supplements (0.6 meq/kg/d Mg pidolate). Hematological parameters, erythrocyte Na, K, and Mg content, erythrocyte density, membrane transport of Na and K, and osmotic gradient ektacytometry were measured. We found significant increases in sickle erythrocyte Mg and K content and reduction in the number of dense sickle erythrocytes. Erythrocyte K-Cl cotransport was reduced significantly. We also observed a significant reduction in the absolute reticulocyte count and in the number of immature reticulocytes. Ektacytometric analysis showed changes indicative of improved hydration of the erythrocytes. There were no laboratory or clinical signs of hypermagnesemia. Mild, transient diarrhea was the only reported side effect. We conclude that oral Mg supplementation reduces the number of dense erythrocytes and improves the erythrocyte membrane transport abnormalities of patients with sickle cell disease.

Adolescent↗
PubMed1997

Removal of erythrocyte membrane iron in vivo ameliorates the pathobiology of murine thalassemia.

Abnormal deposits of free iron are found on the cytoplasmic surface of red blood cell (RBC) membranes in beta-thalassemia. To test the hypothesis that this is of importance to RBC pathobiology, we administered the iron chelator deferiprone (L1) intraperitoneally to beta-thalassemic mice for 4 wk and then studied RBC survival and membrane characteristics. L1 therapy decreased membrane free iron by 50% (P = 0.04) and concomitantly improved oxidation of membrane proteins (P = 0.007), the proportion of RBC gilded with immunoglobulin (P = 0.001), RBC potassium content (P < 0.001), and mean corpuscular volume (P < 0.001). Osmotic gradient ektacytometry confirmed a trend toward improvement of RBC hydration status. As determined by clearance of RBC biotinylated in vivo, RBC survival also was significantly improved in L1-treated mice compared with controls (P = 0.007). Thus, in vivo therapy with L1 removes pathologic free iron deposits from RBC membranes in murine thalassemia, and causes improvement in membrane function and RBC survival. This result provides in vivo confirmation that abnormal membrane free iron deposits contribute to the pathobiology of thalassemic RBC.

Animals↗
PubMed1997

Low concentrations of nitric oxide increase oxygen affinity of sickle erythrocytes in vitro and in vivo.

The hallmark of sickle cell disease (SCD) is the polymerization of deoxygenated sickle hemoglobin (HbS). In SCD patients, one strategy to reduce red blood cell (RBC) sickling is to increase HbS oxygen affinity. Our objective was to determine if low concentrations of nitric oxide (NO) gas would augment the oxygen affinity of RBCs containing homozygous HbS (SS). Blood containing normal adult hemoglobin (AA) or SS RBCs was incubated in vitro in the presence of varying concentrations of NO up to 80 ppm, and oxygen dissociation curves (ODCs) were measured. In addition, blood was obtained from three AA and nine SS volunteers, before and after breathing 80 ppm NO in air for 45 min, and the ODCs were measured. Exposure of SS RBCs to 80 ppm NO in vitro for 5 min or longer decreased the partial pressure of oxygen at which hemoglobin is 50% saturated with oxygen (P50), an average of 15% (4.8+/-1.7 mmHg mean+/-SE; P < 0.001). The increase in SS RBC oxygen affinity correlated with the NO concentration. The P50 of AA RBCs was unchanged (P > 0.1) by 80 ppm NO. In SS volunteers breathing 80 ppm NO for 45 min, the P50 decreased (P < 0.001) by 4.6+/-2.0 mmHg. 60 min after NO breathing was discontinued, the RBC P50 remained decreased in five of seven volunteers in whom the ODC was measured. There was no RBC P50 change (P > 0.1) in AA volunteers breathing NO. Methemoglobin (Mhb) remained low in all subjects breathing NO (SS Mhb 1.4+/-0.5%), and there was no correlation (r = 0.02) between the reduction in P50 and the change in Mhb. Thus, low concentrations of NO augment the oxygen affinity of sickle erythrocytes in vitro and in vivo without significant Mhb production. These results suggest that low concentrations of NO gas may offer an attractive new therapeutic model for the treatment of SCD.

Adolescent↗
PubMed1997

Dietary magnesium supplementation ameliorates anemia in a mouse model of beta-thalassemia.

To ascertain the quantitative effect on the disease beta-thalassemia of a low-magnesium (Mg) diet compared with a high-Mg diet and a standard-Mg diet, we studied the effect these diets had over a 4-week period on beta-thalassemic (beta thal) mice compared with normal C57BL/6 mice used as controls. The low-Mg diet consisted of 6 +/- 2 mg Mg/kg body weight/d, the high-Mg diet 1,000 +/- 20 mg Mg/kg body weight/d, and the standard-Mg diet 400 +/- 20 mg Mg/kg body weight/d. Beta thal mice that were fed the low-Mg diet became more anemic, had reduced serum and erythrocyte Mg, and had decreased erythrocyte K. Their K-Cl cotransport increased, followed by commensurate cell dehydration. The high-Mg group showed a significant improvement of the anemia, increased serum and erythrocyte Mg, increased erythrocyte Mg, increased erythrocyte K, reduced K-Cl cotransport, and diminished cell dehydration. C57BL/6 control mice that received the low-Mg diet experienced anemia with erythrocyte dehydration, whereas the high-Mg diet had little effect on the hematologic parameters. Beta thal and C57BL/6 control mice that were fed a standard diet showed no changes. These results indicate that dietary Mg supplementation corrects hypomagnesemia and improves anemia in murine beta thal and should be assessed in human beta-thalassemia.

Animals↗
PubMed1997

The antifungal imidazole clotrimazole and its major in vivo metabolite are potent blockers of the calcium-activated potassium channel in murine erythroleukemia cells.

Clotrimazole (CLT), a member of the antifungal imidazole family of compounds, has been found to inhibit both calcium (Ca2+)-activated 86Rb and potassium (K) fluxes of human red cells and to inhibit red cell binding of 125I-charybdotoxin (ChTX) [11]. We have now used patch-clamp techniques to demonstrate reversible inhibition of whole cell KCa2+ currents in murine erythroleukemia (MEL) cells by submicromolar concentrations of CLT. Inhibition was equivalent whether currents were elicited by bath application of the Ca2+ ionophore A23187 or by dialyzing cells with a pipette solution containing micromolar concentrations of free Ca2+. The extent of inhibition of whole cell MEL KCa2+ currents was voltage-dependent, decreasing with increasing test potential. We also determined the single channel basis of the CLT inhibition in MEL cells by demonstrating the inhibition of a calcium-activated, ChTX-sensitive K channel by CLT in outside-out patches. The channel was also blocked by the des-imidazolyl metabolite of CLT, 2-chlorophenyl-bisphenyl-methanol (MET II) [15], thus demonstrating that the imidazole ring is not required for the inhibitory action of CLT. Single KCa2+ channels were also evident in inside-out patches of MEL cells. Block of K current by CLT was not unique to MEL cells. CLT also inhibited a component of the whole cell K current in PC12 cells. Channel specificity of block by CLT was determined by examining its effects on other types of voltage-sensitive currents. CLT block showed the following rank order of potency: K currents in PC12 cells > Ca2+ currents in PC12 cells >> Na currents in sympathetic neurons. These results demonstrate that direct inhibition of single KCa2+ by CLT can be dissociated from inhibition of cytochrome P-450 in MEL cells.

Animals↗
PubMed1997

Characterization of adult alpha- and beta-globin genes in the zebrafish.

Developmental switching of hemoglobins (Hbs) occurs in most vertebrates, yet the cellular and molecular basis for this process remains elusive. The zebrafish is a new genetic and developmental system that can be used to study embryogenesis, and mutants with a variety of defects in hematopoiesis have recently been derived. To initiate our studies on Hb switching in this organism, we have characterized the globins expressed in the adult. Reversed-phase high performance liquid chromatography and mass spectrometric analyses of adult peripheral blood hemolysates showed that there are three major alpha globins and two beta globins in circulating erythroid cells. In addition, we have isolated and characterized zebrafish adult alpha- and beta-globin cDNA clones that encode some of these globins. High levels of alpha- and beta-globin gene expression were detected in adult erythroid cells, whereas embryonic erythroid cells expressed little, if any, of these RNAs. We have also shown that the alpha- and beta-globin genes are tightly linked on the same chromosome and are arrayed in a 3'-5' to 5'-3' configuration, respectively. The characterization of these genes and regulatory elements in this globin locus will provide insight into the process of globin gene transcription. With these reagents, future studies of Hb switching in zebrafish mutants with defective hematopoiesis will be possible.

Amino Acid Sequence↗
PubMed1997

The effect of intravenous iron on the reticulocyte response to recombinant human erythropoietin.

We studied the effect of intravenous (i.v.) administration of 200 mg of iron sucrose following an i.v. bolus injection of recombinant human erythropoietin (r-HuEPO; 300 U/kg body weight) in seven subjects and compared it with seven subjects treated with r-HuEPO alone. Reticulocytes, serum erythropoietin (EPO) and ferritin levels were studied at baseline and daily for the following 8 d. Use of i.v. iron abolished the marked reduction in serum ferritin observed with r-HuEPO administration. Although the total number of reticulocytes was not affected by i.v. iron administration, the reticulocyte Hb content and retHb (a measure in g/l of the Hb contained in all reticulocytes) were increased in the i.v. iron/r-HuEPO group compared with the group who received r-HuEPO alone. Therefore i.v. iron significantly potentiates the haemopoietic response to r-HuEPO in normal subjects.

Adult↗
PubMed1997

Cellular effects of hydroxyurea in Hb SC disease.

Hb S polymerizes in high-density Hb SC disease erythrocytes. We hypothesized that hydroxyurea -- perhaps independent of increasing Hb F -- might reduce the density of these cells. Six Hb SC disease patients were given 1000mg of hydroxyurea daily and blood counts, cell volumes, and cell density were followed for 12 months. There was an increase in MCV and reticulocyte MCV. A fall in absolute reticulocyte counts, high-staining ('stress') reticulocytes, serum bilirubin, and an increase in the ratio of mature red cell haemoglobin to reticulocyte haemoglobin, coupled with a rise in the haematocrit inferred a decrease in haemolysis and 'stress erythropoiesis'. An improvement in cell hydration was suggested by a reduction in reticulocyte mean cell haemoglobin concentration (CHCMr), red cells and reticulocytes with CHCM > 38, and decreased dense cell counts estimated by phthalate ester and Percoll-Larex gradients. After 4-5 months treatment, Hb F rose in a few patients but the overall difference in pre- and post-treatment Hb F was not significant. A decline in cell density should diminish the polymerization tendency of Hb S in Hb SC disease.

Anemia, Sickle Cell↗
PubMed1997

Degree of agreement in plasma fibrinogen among two functional and one immunonephelometric assays.

The purpose of this study was to assess the interchangeability of the nephelometric (immunoassay), von Clauss, and optical (derived) fibrinogen assays. When the nephelometric assay was compared with either of the two functional assays (199 samples) and when the von Clauss and optical methods were compared (879 samples), Pearson and intraclass correlations were .96 to .97. However, there were statistically significant biases (P < .001); the mean ratios of nephelometric to functional assay values were 1.05 to 1.07, and the mean optical to von Clauss assay ratio was 1.05 (data analyzed as logs and expressed as antilogs). The 95% limits of agreement demonstrated that 5% of the ratios for the von Clauss and optical methods were outside the 0.83 to 1.32 range. Analyses restricted to cases with a fibrinogen value of less than 2.0 g/L resulted in somewhat greater biases and higher upper limits of agreement. Laboratorians need more than correlations to make informed judgments regarding the interchangeability of these methods.

Fibrinogen↗
PubMed1997

Reticulocyte hemoglobin: an integrated parameter for evaluation of erythropoietic activity.

Traditional reticulocyte counts provide only a partial estimate of the erythropoietic bone marrow activity and do not account for qualitative variations of reticulocyte cellular indexes and hemoglobin content in particular. We have studied a new integrated parameter, reticulocyte hemoglobin (retHb), that quantifies in grams per liter the hemoglobin contained in the circulating reticulocyte compartment and is obtained by multiplying the absolute reticulocyte count and the reticulocyte cell hemoglobin content. In 50 normal control subjects, retHb values were 1.76 +/- 0.59 g/L. The retHb values were lower in patients double heterozygous for HbS and HbC (SC disease) (3.33 +/- 1.52 g/L, n = 13) compared with homozygous HbS disease (SS) with concomitant alpha-thalassemia (5.27 +/- 1.51 g/L and 5.48 +/- 1.06 g/L for 12 patients with 3 alpha-genes and 3 patients with 2 alpha-genes, respectively) and to SS disease with no alpha-thalassemia (6.47 +/- 3.05, n = 20). The hemoglobin contained in the red blood cell pool (rbcHb) also can be calculated by subtracting retHb from the total hemoglobin. The ratio between the two pools (rbcHb/retHb, normal value 76.6 +/- 21.9, n = 50) provides a rough estimate of red blood cell survival. It was 9.8 +/- 4.1 in SS disease, 16.2 +/- 10.1 and 14.7 +/- 5.0 in SS disease with 3 and 2 normal alpha-genes, respectively, and 36.6 +/- 17.8 in SC disease with no alpha-thalassemia. We also studied retHb in patients receiving hydroxyurea therapy for SS disease, intravenous or oral iron for iron deficiency, or recombinant human erythropoietin (r-HuEPO) therapy. All these conditions are characterized by changes in reticulocyte counts and marked variations in reticulocyte cellular hemoglobin contents, which can be integrated into the retHb parameter. Measurement of retHb and the rbcHb/retHb ratio may provide an estimate of the reduction in red blood cell survival and the severity of hemolysis in various anemias and allow more precise monitoring of the response to hydroxyurea, iron, r-HuEPO, or other therapies.

Administration, Oral↗
PubMed1997

Erythrocyte membrane transport physiology.

Several transport pathways are involved in the regulation of cell volume and ion content in the human erythrocyte. Studies of these pathways have shown that K-Cl contransport and the Ca-gated K channel (Gardos channel) play an important role in the dehydration of sickle erythrocytes. Therapeutic strategies based on the specific blockade of these pathways have been tested in transgenic sickle mice and in patients with sickle cell disease, using oral Mg pidolate to inhibit K-Cl cotransport and oral clotrimazole to inhibit the Gardos channel. Studies on the erythrocyte Na-H (Na-Li) exchanger have uncovered an important role for insulin and blood pressure in mediating the activity of this pathway. These findings explain the reports of abnormal Na-Li exchange in diabetic nephropathy and essential hypertension. Targeted mutagenesis of the anion exchanger protein band 3 in mice has demonstrated that absence of this protein is compatible with life and leads to severe hemolytic anemia, normal assembly of the cytoskeleton, and reduced mechanical stability of the erythrocyte. Identification of the molecular identity of all the major erythrocyte transporters is imminent and will provide the bases for future studies of these proteins in the normal and abnormal erythrocyte.

Animals↗
PubMed1997

Cerebrospinal fluid plasminogen activator inhibitor-1: a prognostic factor in posthaemorrhagic hydrocephalus.

Intraventricular fibrinolytic enhancement with plasminogen activators is an experimental treatment for posthaemorrhagic hydrocephalus, but some infants do not respond. The objectives of this study were to investigate whether plasminogen activator inhibitor-1 is detectable in normal or posthaemorrhagic neonatal cerebrospinal fluid and whether higher neonatal cerebrospinal fluid concentrations of plasminogen activator inhibitor-1 are associated with failure of fibrinolytic therapy. Cerebrospinal fluid samples from 7 controls and 16 infants with posthaemorrhagic hydrocephalus (15 treated with exogenous fibrinolytic agents) were analysed for plasminogen activator inhibitor-1. Plasminogen activator inhibitor-1 was not detectable in any of the control samples but was detectable in all but one of the posthaemorrhagic samples, and at significantly higher levels in the treatment failures (median 94 ng ml(-1)) than in the treatment successes (median 25 ng ml(-1)). High levels of plasminogen activator inhibitor-1 in the cerebrospinal fluid are predictive of, and provide a plausible biological explanation for, failure of intraventricular fibrinolytic therapy.

Brain Damage, Chronic↗
PubMed1997

Reinterpretation of the RACTK1 K+ channel.

The RACTK1 cDNA cloned from rabbit kidney cortical collecting duct cells was associated with inwardly rectifying pH-regulated K+ channel activity (M. Suzuki, K. Takahashi, M. [keda, H Hayakawa, A. Ogawa, Y. Kawaguchi, and O. Sakai. Nature Lond. 367: 642-645, 1994). The deduced amino acid sequence of the encoded novel polypeptide lacked the signature sequence of a K(+)-selective pore region but predicted a topography suggestive of the inward rectifier K+ channel family. In subsequent articles a RACTK1 epitope was immunolocalized to the apical surface of kidney collecting duct and to arteriolar smooth muscle [M. Suzuki, T. Takigawa, K. Kimura, C. Koseki, and M. Imai. Am. J. Physiol. 269 (Cell Physiol, 38): C496-C503, 1995], and apamin-sensitive K+ currents displaying Ca(2+)-dependent and voltage-independent activation accompanied stable heterologous overexpression of RACTK1 [M. Suzuki, M. Murata, M. Ikeda, T. Miyoshi, and M. Imai. Am. J. Physiol. 270 (Cell Physiol, 39): C964-C968, 1996]. We now report that the "RACTK1" open reading frame is a frame-shifted translation of the antisense strand of an Escherichia coli gene member of a coenzyme A transferase gene family. "RACTK1" mRNA was absent from tissues free of E. coli contamination, and the "RACTK1" gene was undetectable in Southern blots of human and rabbit genomic DNA. We conclude that the immunostaining patterns and Ca(2+)-activated K+ channel activity heretofore attributed to RACTK1 must be otherwise explained.

Animals↗
PubMed1997

Inhibition of maxi-K currents in ferret portal vein smooth muscle cells by the antifungal clotrimazole.

The antifungal agent clotrimazole (CLT) is a potent small-molecule inhibitor of Ca-activated K (KCa) currents of intermediate conductance in murine erythroleukemia cells. This study demonstrates that CLT also inhibits large-conductance KCa currents (maxi-K currents) in acutely dissociated vascular smooth muscle (VSM) cells of ferret portal vein. The magnitude of block of a component of the whole cell K current by CLT was sensitive to test potential. CLT inhibited unitary maxi-K currents in outside-out patches, apparently by decreasing the mean open time. A metabolite of CLT lacking an imidazole ring also inhibited K currents. In contrast, the antifungal drug ketoconazole increased these same currents. Thus the inhibitory action of CLT appears to be due to a direct interaction with the channel protein rather than to imidazole block of cytochrome P-450 activity. Consistent with inhibition of maxi-K currents by CLT, superfusion of strips of portal vein VSM with CLT enhanced isometric tension and spontaneous rate of contraction, suggesting that CLT modulation of maxi-K currents may alter vasomotor functioning.

4-Aminopyridine↗