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Biomedical subjects

Yang Li

Publications and source records attributed to Yang Li.

At least 199 records · Page 11Linked to original sources
PubMed2003

Long-term effects of imidapril on calcium and potassium currents in rabbit left ventricular hypertrophic myocytes.

OBJECTIVE: To investigate the long-term effects of imidapril (IMI) on action potential and calcium and potassium currents in rabbit left ventricular hypertrophic myocytes. METHODS: Rabbits were randomly divided into three groups: IMI-treated, hypertrophic and sham-operated control groups. Cardiac hypertrophy was induced in hypertrophy group by partial ligation of the abdominal aorta. In the IMI-treated group, the rabbits were administered IMI (1.5 mg x kg(-1) x d(-1)) for 8 weeks after surgery. In the sham-operated control group, the animals underwent an abdominal laparotomy without further procedure. Whole-cell patch clamp technique was used to record ionic currents. RESULTS: Membrane capacitance was larger in hypertrophic cells than in sham-operated cells or IMI-treated cells. Action potential duration was lengthened in hypertrophic cells and was remarkably shortened by IMI. The density of ICa, L was reduced from 12.8 +/- 0.7 pA/pF in the sham-operated cells, to 7.7 +/- 0.8 pA/pF in hypertrophic cells, while it resembled the control cells after IMI treatment (11.9 +/- 1.0 pA/pF). After IMI treatment, the density of I(Ks,tail) was enhanced from 2.5 +/- 0.1 pA/pF in hypertrophic cells to 4.7 +/- 0.6 pA/pF (n = 7, P < 0.01), which was similar to the sham-operated cells. The densities of Ito and IK1 were significantly increased in IMI-treated cells, from 3.8 +/- 0.4 pA/pF and 3.7 +/- 0.5 pA/pF in the hypertrophic cells to 6.4 +/- 0.8 pA/pF and 6.5 +/- 0.3 pA/pF, respectively, but the IKr densities were not different in the three groups. CONCLUSION: IMI could reverse the increase in membrane capacitance in hypertrophic cells, shorten action potential duration, and increase the densities of ICa, L, IKs, Ito and IK1 in hypertrophic cells.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2003

[The expansion and biological characteristics of human mesenchymal stem cells].

OBJECTIVE: Mesenchymal stem cells (MSCs) were adult stem cells which contribute to the regeneration of mesenchymal tissues such as bone cartilage, muscle, ligament, tendon, adipose and stroma. Due to the multipotential ability and self-renewal capacity, the mesenchymal stem cells can be applied in many fields, such as the seed cells in tissues engineering, cell therapy and gene therapy. To enhance the clinical use of MSCs, the investigators studied the isolation and expansion of MSCs from adult bone marrow, fetal bone marrow and human umbilical cord blood, and investigated their biological identities. METHODS: Two kinds of incubation systems containing L-DMEM or MSC special culture medium were used to purify and expand MSCs. The growth, purification and proliferative abilities of 3 kinds of MSCs were observed and their immunophenotypes were determined by flow-cytometry. RESULTS: (1) The shapes of 3 kinds of cells were same. There was no difference in number and size. The colonies formed early in adult bone marrow MSCs. (2) There was no difference in the expansion speed of the 3 kinds of MSCs, but after the colonies confluenced there had no touching constrain in MSCs from umbilical cord blood and fetal bone marrow. When the colonies confluenced, the cells also had proliferation ability. But in adult bone marrow, the touching constrain was significant. (3) MSCs had strong self-renewal capacity. After primary culture approximately 5 - 6 x 10(5) MSCs were obtained from 8 x 10(6) MNC of bone marrow and 25 x 10(6) MNC of umbilical cord blood. After passage 3, passage 5 and passage 10, the investigators could get 10(7), 10(8) and 10(10) MSCs, respectively. (4) Along with the increase in the passage and prolonging of culture time, the ability of expansion decreased, but they maintained good puripotentiality. After passage 2, passage 3 and passage 5, the purity of MSCs was 90%, 95% and 99%, respectively. (5) Three kinds of MSCs were all positive for CD(29), CD(44), CD(59), CD(90), CD(105), CD(166) and all negative for the markers of hematopoietic cells such as CD(11a), CD(14), CD(33), CD(34), CD(28), CD(45). All the important GVHD correlation markers were negative, such as HLA-DR, B7-1 (CD(80)), B7-2 (CD(86)), CD(40) and CD(40L). There were no differences in the phenotype among the 3 kinds of MSCs cells. (6) The 2 kinds of culture mediums used did not markedly affect isolation and expansion of MSCs, and the biological properties of MSCs. CONCLUSIONS: (1) Human MSCs could be isolated from many kinds of human tissues, and they had no difference in their origin; (2) Human MSCs maintained good puripotentiality and self-renewal capacity. Therefore, they could meet with the need of clinical tissue engineering. (3) The negative GVHD correlated markers might result from the fact that MSCs had no HLA barrier but had broad clinical use.

Bone Marrow Cells↗
PubMed2003

[Clinical analysis of 29 children with early infectious complications following hematopoietic stem cells transplantation].

OBJECTIVE: To study the clinical features and the incidence of early infectious complications following children hematopoietic stem cells transplantation (HSCT). METHODS: The clinical data of 29 cases with early infectious complications following HSCT was retrospectively analyzed. RESULTS: The incidence of early infectious complications following HSCT in 31 children (including 22 cord blood transplantation and 9 peripheral blood stem cells transplantation) was 94% (29/31). The first occurrence of the early infectious complications was at a median of 6 (0 - 22) days, the peak time of incidence was at a median of 4 - 7 days post transplantation. The duration of the first early infectious complications was at a median of 9 (3 - 20) days. The occurrence of the second early infectious complications was at a median of 19 (13 - 27) days. For all of the 29 children, when they developed early infectious complications their absolute neutrophil counts (ANC) were all > 0.5 x 10(9)/L. The most common infectious sites were the digestive tract (oral and gastro-intestinal mucositis) and then the respiratory tract. Gram negative blood infections were quite frequent and Pseudomonas aeruginosa was common in the oral-pharynx discharge cultures. Two children had Mycoplasma pneumonia infections and there were 4 incidences with fever but no definite infectious foci. The incidence and duration of early infectious complications following hematopoietic stem cells transplantation were associated with the duration of neutropenia. The source and the MNCs dose of the graft, the difference of conditioning regimen and GVHD prophylaxis method did not have a significant impact on the incidence and duration of early infectious complications. Antibiotic prophylaxis (including Tienam) could delay the occurrence of the early infections significantly. CONCLUSION: The incidence and duration of early infectious complications following hematopoietic stem cells transplantation were directly associated with the duration of neutropenia. Tienam regimen could postpone the early infections incidence and had effect of preventing the early infectious complications.

Adolescent↗
PubMed2003

[Urinary excretion pattern of 2-thio-thiazolidine-4-carboxylic acid in workers exposed to carbon disulfide].

OBJECTIVE: To study the urinary excretion pattern for of 2-thio-thiazolidine-4-carboxylic acid (TTCA) in workers exposed to CS2, so as to provide experimental basis for working out biomonitoring measures for short-term exposure to CS2. METHODS: Sixty-nine subjects were divided into three groups: (1) fourteen volunteers who had not been exposed to CS2 before were exposed to CS2 for 2 hours, their urine samples were collected and analyzed at different time points; (2) The urine samples of 15 occupational exposure workers were collected on pre-shift, mid-shift, post-shift; (3) The relationship between 8 h time weighted average CS2 exposure concentrations (PC-TWA) and TTCA levels of post-shift urine was studied among 40 workers chronically exposed to CS2. RESULTS: (1) In the 1st group, urine TTCA level reached the peak [(1.03 +/- 0.72) mg/gCr] 4 h after exposure; (2) In the 2nd group, urine TTCA level on pre-shift [(0.37 +/- 0.28) mg/gCr] was lower than that on mid-shift [(1.23 +/- 0.71) mg/gCr, P<0.01] and post-shift [(1.31 +/- 0.78) mg/gCr, P<0.01]; (3) In the 3rd group, there was a linear relationship between the post-shift urine TTCA level and 8 h CS2 exposure concentrations dose (PC-TWA). The regression equation is Y(TTCA mg/gCr)=1.163 6X(CS2 mg/m3)-5.411 6. CONCLUSION: The post-shift urine TTCA levels may be regarded as a bio-monitoring index for workers exposed to CS2.

Adult↗
PubMed2003

[Effect of atmospheric CO2 enrichment on soil microbes and related factors].

This paper summarized the effects of atmospheric CO2 enrichment on soil microbes and their related factors, including soil microflora, soil respiration, soil microbial biomass, and higher plant-microbe symbiosis. The factors related to soil microbic activity such as litter decomposition, root exudates, soil nutrient availability, nutrient use efficiency and soil fauna were also affected by the CO2 enrichment.

Air↗
PubMed2002

[Heterogeneity of action potential and ion currents in the left ventricular myocytes of the rabbit].

Experiments were performed to investigate the heterogeneity of the action potential and ion currents in left ventricular myocytes of the rabbit. Myocytes were isolated by enzymatic method. The sub-endocardial (Endo) and sub-epicardium (Epi) tissues were separated from the other region (midmyocardium, M) with a razor. Single cells in each region were obtained by gentle shaking and dispersing in a chamber filled with normal Tyrode's solution. The results showed that the action potential and the ion currents in the three layers were significantly different. M cells had a more pronounced spike-and-dome configuration, with a significantly larger phase 1 magnitude and plateau voltage. Action potential duration (APD) in M cells was longer than that in Epi or Endo cells. I(Ca, L) and I(to) in M cells were higher than those of Epi and Endo. On the contrary, I(K,s) in M cells was the minimum compared with those in the three LV walls. The differences in ion currents may well explain the heterogeneity of action potentials in M layers of the rabbit heart.

Action Potentials↗
PubMed2002

Tissue-specific structure/function differentiation of the liver isoform of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase.

The crystal structures of the human liver 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase in three different liganding states were determined and compared with those of the rat testis isozyme. A set of amino acid sequence heterogeneity from the two distinct genes encoding the two different tissue isozymes leads to both global and local conformational differences that may cause the differences in catalytic properties of the two isozymes. The sequence differences in a beta-hairpin loop in the kinase domain causes a translational shift of several hydrophobic interactions in the dimeric contact region, and its propagation to the domains interface results in a 5 degrees twist of the entire bisphosphatase domain relative to the kinase domain. The bisphosphatase domain twist allows the dimeric interactions between the bisphosphatase domains, which are negligible in the testis enzyme, and as a result, the conformational stability of the domain is increased. Sequence polymorphisms also confer small but significant structural dissimilarities in the substrate-binding loops, allowing the differentiated catalytic properties between the two different tissue-type isozymes. Whereas the polymorphic sequence at the bisphosphatase-active pocket suggests a more suitable substrate binding, a similar extent of sequence differences at the kinase-active pocket confers a different mechanism of substrates bindings to the kinase-active pocket. It includes the ATP-sensitive unwinding of the switch helix alpha5, which is a characteristic ATP-dependent conformational change in the testis form. The sequence-dependent structural difference disallows the liver kinase to follow the ATP-switch mechanism. Altogether these suggest that the liver isoform has structural features more appropriate for an elevated bisphosphatase activity, compared with that of the testis form. The structural predisposition for bisphosphatase activity in the liver isozyme is consistent with the liver-unique glucose metabolic pathway, gluconeogenesis.

Amino Acid Sequence↗
PubMed2002

Huperzine A inhibits the sustained potassium current in rat dissociated hippocampal neurons.

The actions of huperzine A (HupA), a novel cholinesterase inhibitor, on the sustained potassium current were investigated in acutely dissociated hippocampal neurons of rat. HupA inhibited the current (IC(50) = 856 +/- 1 microM) with voltage-dependency. The effect was insensitive to 3 microM atropine. Tacrine (IC(50) = 43 +/- 3 microM) was 20 times more potent than HupA. HupA hyperpolarized the activation curve of the current by 16 mV, and markedly prolonged the decay time constant tau(2). HupA affected neither the steady-state inactivation of the current, nor its recovery from inactivation. The potential relevance of the inhibitory effect of HupA on the current to the treatment of Alzheimer's disease is discussed.

Alkaloids↗
PubMed2002

Huperzine A, a nootropic agent, inhibits fast transient potassium current in rat dissociated hippocampal neurons.

The actions of huperzine A (HupA), a novel cholinesterase inhibitor, on the fast transient potassium current (IA) were investigated in CA1 pyramidal neurons acutely dissociated from rat hippocampus. HupA reversibly inhibited IA (IC(50) = 914 +/- 1 microM). The effect was voltage-independent and insensitive to atropine. Tacrine was eight times more potent than HupA (IC(50) = 115 +/- 2 M), whereas huperzine B had little effect. HupA slowed down the decay of IA and its recovery from inactivation. HupA had no effect on the steady-state inactivation, but hyperpolarized the activation curve of IA by 6 mV. The results suggest that HupA may act as a blocker at the external mouth of the A channel. The potential relevance of the inhibitory effect of HupA on IA to the treatment of Alzheimer's disease has been discussed.

Acetylcholine↗
PubMed2002

T0070907, a selective ligand for peroxisome proliferator-activated receptor gamma, functions as an antagonist of biochemical and cellular activities.

The nuclear hormone receptor peroxisome proliferator-activated receptor gamma (PPARgamma (NR1C3)) plays a central role in adipogenesis and is the molecular target for the thiazolidinedione (TZD) class of antidiabetic drugs. In a search for novel non-TZD ligands for PPARgamma, T0070907 was identified as a potent and selective PPARgamma antagonist. With an apparent binding affinity (concentration at 50% inhibition of [(3)H]rosiglitazone binding or IC(50)) of 1 nm, T0070907 covalently modifies PPARgamma on cysteine 313 in helix 3 of human PPARgamma2. T0070907 blocked PPARgamma function in both cell-based reporter gene and adipocyte differentiation assays. Consistent with its role as an antagonist of PPARgamma, T0070907 blocked agonist-induced recruitment of coactivator-derived peptides to PPARgamma in a homogeneous time-resolved fluorescence-based assay and promoted recruitment of the transcriptional corepressor NCoR to PPARgamma in both glutathione S-transferase pull-down assays and a PPARgamma/retinoid X receptor (RXR) alpha-dependent gel shift assay. Studies with mutant receptors suggest that T0070907 modulates the interaction of PPARgamma with these cofactor proteins by affecting the conformation of helix 12 of the PPARgamma ligand-binding domain. Interestingly, whereas the T0070907-induced NCoR recruitment to PPARgamma/RXRalpha heterodimer can be almost completely reversed by the simultaneous treatment with RXRalpha agonist LGD1069, T0070907 treatment has only modest effects on LGD1069-induced coactivator recruitment to the PPARgamma/RXRalpha heterodimer. These results suggest that the activity of PPARgamma antagonists can be modulated by the availability and concentration of RXR agonists. T0070907 is a novel tool for the study of PPARgamma/RXRalpha heterodimer function.

3T3 Cells↗
PubMed2002

Butterfly-shaped pattern dystrophy: a genetic, clinical, and histopathological report.

OBJECTIVES: To identify the disease-causing mutation in a large family segregating dominantly inherited butterfly-shaped pattern dystrophy (BPD) and to describe the microscopic pathological changes observed in a member of this family. METHODS: Seventeen individuals at risk for dominantly inherited BPD in a family were examined and blood samples obtained. Linkage analysis and mutation screening of the human retinal degeneration slow (RDS)/peripherin locus were performed. Light and electron microscopic examinations were performed on 1 postmortem eye of 1 affected individual. RESULTS: Four individuals demonstrated macular degenerative changes with diminished visual acuity, and 3 others exhibited early signs of atrophy without visual deficits. Microscopic examination of the left eye of 1 patient revealed an area of total loss of the retinal pigment epithelium (RPE) and photoreceptor cell layer with intact choriocapillaris and lipofuscin-containing cells in the subretinal space. Outside the area of RPE atrophy, the RPE was greatly distended by lipofuscin. The disease locus in this family was mapped to 6p21.2, the region of the RDS/peripherin gene. Further analysis identified a G-->A change at nucleotide position 637 of RDS/peripherin, predicting a novel Cys213Tyr substitution in all affected members of the family. CONCLUSIONS: This study describes a new RDS/peripherin mutation for BPD and provides the first combined genetic-pathological study of this condition, to our knowledge. CLINICAL RELEVANCE: Accumulation of lipofuscin in RPE is a prominent feature of several retinal disorders, including age-related macular degeneration. Further elucidation of the cellular and molecular mechanism of BPD may provide insight into pathogenesis and lead to novel treatment approaches for this and other macular degenerations.

Adult↗
PubMed2002

The role of selectins and integrins in adenovirus vector-induced neutrophil recruitment to the liver.

Adenovirus vectors for human gene therapy induce early host inflammatory responses in transduced tissues that limit gene transfer efficiency and can result in significant morbidity. The present study aimed to elucidate the cellular mechanisms underlying the acute inflammation induced by adenovirus vectors in the liver. Leukocyte rolling and adhesion in response to an intravenously administered adenovirus vector was examined by intravital microscopy in mouse liver. Adenovirus vectors significantly increased leukocyte rolling and adhesion in the postsinusoidal venules within minutes of transduction. Unlike other inflammatory states in the liver, no leukocyte retention was seen in the sinusoids in response to adenovirus vector administration. Inhibition of P-selectin, alpha(4)-integrin, and E-selectin was necessary to completely block leukocyte rolling and subsequent adhesion. The administration of an anti-alpha(4)-integrin antibody alone significantly reduced leukocyte adhesion. In contrast, adenovirus vector-induced leukocyte adhesion was unchanged in CD18-knockout mice. Depletion of circulating neutrophils eliminated leukocyte rolling and adhesion in response to adenovirus vector transduction in the liver. In conclusion, adenovirus vectors induce rapid neutrophil-mediated inflammation in the post-sinusoidal venules by selectins and alpha(4)-integrin but surprisingly not by CD18.

Adenoviridae↗
PubMed2002

Comparison of three DNA marker systems for assessing genetic diversity in Asian arowana (Scleropages formosus).

Three DNA marker systems -- random amplified polymorphic DNA (RAPD), amplified fragment length polymorphism (AFLP) and microsatellites -- were used to estimate the genetic diversity in Asian arowana (Scleropages formosus) by genotyping fish individuals from three different sources. Parallel application of the three DNA marker systems allowed us to compare their utility for the analysis of genetic diversity. Microsatellites displayed the highest expected heterozygosity, whereas the values obtained by RAPD and AFLP were much lower. Multiplex ratio and marker index were higher for AFLP than for RAPD or microsatellites. Weak correlation was detected between genetic similarity estimated from data obtained with the three DNA marker systems: estimates from RAPD and AFLP data turned out to be higher than those from microsatellites. On the other hand genetic similarity was higher in the red variety than in the green one, especially when tested with microsatellites. Based on the genetic distance matrices calculated from microsatellite analysis, all red individuals were clustered into one group, whereas only a subset of them was clustered when either RAPD or AFLP was used. This indicated that the microsatellite system detected population subdivision more efficiently than either RAPD or AFLP.

Animals↗
PubMed2002

An X-prolyl dipeptidyl aminopeptidase from Lactococcus lactis: cloning, expression in Escherichia coli, and application for removal of N-terminal Pro-Pro from recombinant proteins.

A novel pepX gene was cloned from isolated DNA of Lactococcus lactis by PCR. The deduced amino acid sequence of the 89-kDa protein showed 94, 93, 65, and 44% identity with the pepX protein from Lactococcus lactis subsp. cremoris, Lactococcus lactis subsp. lactis, Lactobacillus delbruecki subsp. bulgaricus, and Lactobacillus helveticus, respectively, and contained a serine protease G-K-S-Y-L-G consensus motif. The pepX gene has been cloned into pET17b and was expressed at a high level in Escherichia coli BL21 (DE3) LysS. PepX was purified to approximate homogeneity with ammonium sulfate precipitation and DEAE Sephadex A-50 chromatography. Optimal pepX activity was observed at pH 8.0 and 37 degrees C. According to SDS-PAGE analysis, pepX has a molecular mass of approximately 89 kDa. The peptidase can remove completely the unwanted X-Pro from the N-terminal of the target protein, releasing the naturally active protein and peptide, revealing a prospective application of pepX in large-scale production of pharmaceutical protein and peptide products.

Amino Acid Sequence↗
PubMed2002

Experimental study of the effect of autonomic nervous system on the transmural dispersion of ventricular repolarization under acute myocardial ischemia in vivo.

The effect of the autonomic nerves on the transmural dispersion of ventricular repolarization (TDR) under acute myocardial ischemia in intact canine was investigated. Using the monophasic action potential (MAP) recording technique, MAPs of the epicardium (Epi), mid-myocardium (Mid) and endocardium (Endo) were recorded simultaneously by specially designed plunge-needle electrodes at the left ventricular free wall under acute myocardial ischemia in 12 open-chest dogs. MAPD90 and TDR among three myocardial layers as well as the incidence of the early afterdepolarization (EAD) before autonomic nervous stimulation and during autonomic nervous stimulation were compared. It was found that 10 min after acute myocardial ischemia, TDR was increased from 55 +/- 8 ms to 86 +/- 15 ms during sympathetic stimulation (P < 0.01). The TDR (53 +/- 9 ms) during parasympathetic stimulation was not significantly different from that of the control (55 +/- 8 ms) (P > 0.05). The EAD was elicited in the Mid of 2 dogs (16%) 10 min after acute myocardial ischemia, but the EAD were elicited in the Mid of 7 dogs (58%) during sympathetic stimulation (P < 0.01). It was concluded that: (1) Sympathetic stimulation can increase the transmural dispersion of repolarization and induce early afterdepolarizations in the Mid under acute myocardial ischemia, which provide the opportunity for the ventricular arrhythmia developing; (2) Parasympathetic stimulation has no significant effect on the transmural dispersion of repolarization under myocardial ischemia.

Action Potentials↗
PubMed2002

Novel microsatellites from asian sea bass (Lates calcarifer) and their application to broodstock analysis.

We isolated novel dinucleotide, trinucleotide, and tetranucleotide microsatellites from the genome of Asian sea bass (Lates calcarifer). Two genomic DNA libraries were established, one was enriched for (CA)n repeats, while the other for (GATA)n, (GACA)n, and (AAC)n repeats. Sixty clones containing an insert between 250 and 1000 bp in size were sequenced from each library; altogether 50 (43%) of them contained microsatellites. Forty microsatellites were characterized in 16 unrelated Asian sea bass individuals. Twenty-eight of them (70%) showed specific amplification and polymorphism. The allele number per loci varied between 2 and 20 with an average of 5.3, while expected heterozygosity ranged from 0.31 to 0.95 with an average of 0.64. At some loci allele sizes spread over a wide range (>100 bp). No significant correlation (r = 0.23, df = 31, P > 0.05) was found between the repeat number and the number of alleles. A whole broodstock containing 170 individuals was analyzed by using 8 selected polymorphic microsatellites. The average number of alleles per locus was 11.8 (range, 4-21). The expected heterozygosity ranged from 0.57 to 0.90 with an average of 0.75, while the fixation index was 0.02. Genetic similarity between individuals ranged from 0 to 0.72. Comparison of allele frequencies between the broodstock and the 24 nonrelated individuals revealed some unique alleles.

Journal Article↗
PubMed2002

Effects of benzyltetrahydropalmatine on two components of the delayed rectifier K+ current in Guinea pig ventricular myocytes.

The effects of benzyltetrahydropalmatine (BTHP), a new class III antiarrhythmic agent, on the action potential in guinea pig papillary muscle and the rapidly activating component (I(Kr)) and the slowly activating component (I(Ks)) of the delayed rectifier potassium current (I(K)) in isolated guinea pig ventricular myocytes were investigated. The action potentials of papillary muscles were studied using a standard microelectrode technique, while the K(+) currents were recorded using the whole-cell patch clamp technique. The results showed that BTHP prolonged the action potential duration (APD) without altering other variables of the action potential in guinea pig papillary muscles. The 2 components of I(K) were blocked by BTHP (1 approximately 100 micromol x L(-1)) in time-, concentration-, voltage-, and specifically frequency-dependent fashion. The IC(50) value for blockade of I(Kr) was 13.5 micromol x L(-1), while the IC(50) value for blockade of I(Ks) was 9.3 micromol x L(-1). BTHP 30.0 micromol x L(-1) reduced I(Kr) and I(Kr,tail) by 31 +/- 4.3% and 36 +/- 4.7% (n = 6, p < 0.01) and decreased I(Ks) and I(Ks,tail) by 40 +/- 6.3% and 39 +/- 4.6% (n = 7, p < 0.01) respectively. BTHP accelerated their deactivation course by reducing the time constants of deactivation of I(Kr) and I(Ks). The activation kinetics of I(Kr) or I(Ks) were not affected by BTHP. It is concluded that BTHP prolonged the action potential duration with respect to its non-selective action on I(Kr) and I(Ks) in single guinea pig ventricular cell in a frequency-dependent fashion.

Action Potentials↗