Showing papers by "Hokkaido University published in 1993"

Filling dependence of electronic properties on the verge of metal–Mott-insulator transition in Sr 1 − x La x TiO 3

Abstract: Introducing holes (or partly eliminating electrons) in Mott-Hubbard insulator ${\mathrm{LaTiO}}_{3}$ (with 3${\mathit{d}}^{1}$ configuration) can be carried out by partial substitution of La with Sr, which produces the strongly correlated metallic phase. Systematic variation of electronic properties in ${\mathrm{Sr}}_{1\mathrm{\ensuremath{-}}\mathit{x}}$${\mathrm{La}}_{\mathit{x}}$${\mathrm{TiO}}_{3}$ was investigated as a function of the 3d band filling (x) by measurements of resistivity, Hall coefficient, magnetic susceptibility, and specific heat. Up to the vicinity of the metal-insulator phase boundary (${\mathit{x}}_{\mathit{c}}$\ensuremath{\sim}0.95), ${\mathrm{Sr}}_{1\mathrm{\ensuremath{-}}\mathit{x}}$${\mathrm{La}}_{\mathit{x}}$${\mathrm{TiO}}_{3}$ behaves as a Fermi liquid system where the carrier mass and scattering rate critically increase as the x=1 (${\mathrm{LaTiO}}_{3}$) insulator is approached.

Inverse-dynamics model eye movement control by Purkinje cells in the cerebellum

Abstract: MANY lines of evidence suggest that the cerebellum is involved in motor control1. But what features of these movements are encoded by cerebellar neurons? For slow-tracking eye movements, the activ-ity of Purkinje cells in the ventral paraflocculus of the cerebellum is known to be correlated with eye velocity2–5 and acceleration5. Here we show that the complex temporal pattern of the firing frequency that occurs during the ocular following response elicited by movements of a large visual scene6–8 can be reconstructed by an inverse-dynamics representation, which uses the position, velocity and acceleration of eye movements. Further analysis reveals that the velocity and acceleration components can provide appropriate dynamic drive signals to ocular motor neurons, whereas the position component often has the wrong polarity. We conclude that these Purkinje cells primarily contribute dynamic command signals.

Distinct distributions of five N‐methyl‐D‐aspartate receptor channel subunit mRNAs in the forebrain

Abstract: The distributions of five NMDA receptor channel subunit mRNAs in the mouse forebrain at postnatal day 21 were semiquantitatively examined by in situ hybridization with subunit-specific oligonucleotide probes. In contrast to ubiquitous distribution of the zeta 1 subunit mRNA throughout the forebrain, distributions of four epsilon subunit mRNAs were highly variable from nucleus to nucleus. The telencephalon (except for the septum) expressed the epsilon 1 and epsilon 2 subunit mRNAs. Various combinations of the epsilon 1, epsilon 2, epsilon 3, and epsilon 4 subunit mRNAs were present in different nuclei of the septum, the olfactory bulb, and the thalamus. In the hypothalamus, the suprachiasmatic nucleus expressed distinct signals for the epsilon 3 subunit mRNA alone, whereas other nuclei showed faint signals for the epsilon 1, epsilon 2, and epsilon 4 subunit mRNAs. Moreover, different signal levels of the epsilon subunit mRNAs were found in various regions. The hippocampal CA1 region expressed higher signals for the epsilon 1 and epsilon 2 subunit mRNAs than the CA3 region and the dentate gyrus. In the cerebral cortex, signal levels of the epsilon 1 subunit mRNA were higher in the laminae II/III, IV, and VI than the lamina V, whereas those of the epsilon 2 subunit mRNA were highest in laminae II/III and lowest in laminae IV and V. Different signal levels between the epsilon 1 and epsilon 2 subunit mRNAs were also discerned in the amygdala, the caudate-putamen, and the thalamus. The distinct anatomical distributions and differential signal levels of the epsilon subunit mRNAs strongly suggest different subunit organizations of the NMDA receptor channel in different forebrain neurons, which may result in functional diversity of the channel in vivo.

Effects of coarse woody debris on morphology and sediment storage of a mountain stream system in western Oregon

Abstract: Effects of coarse woody debris (CWD) on channel morphology and sediment storage were investigated at five sites, representative of first-order to fifth-order streams. In the steep and bedrock-confined stream (first-second order), interaction between the channel and CWD was limited, except where breakage upon falling produced CWD pieces shorter than channel width. Channel widening, steepening and sediment storage associated with CWD were observed predominantly in third- to fifth-order streams. Variation in channel width and gradient was regulated by CWD. In the fifth-order stream, most of the CWD pieces derived from the riparian forest interacted directly with the channel without being suspended by sideslopes. In this system CWD promoted lateral channel migration, but sediment storage was temporary, with annual release and capture.

Role of aminopeptidase N (CD13) in tumor-cell invasion and extracellular matrix degradation

Abstract: We have investigated the effect of monoclonal antibodies (MAbs) specific for aminopeptidase N/CD13 on the invasion of human metastatic tumor cells into reconstituted basement membrane (Matrigel). The invasion of human metastatic tumor cells (SN12M renal-cell carcinoma, HT1080 fibrosarcoma and A375M melanoma) into Matrigel-coated filters was inhibited by an anti-CD13 MAb, WM15, in a concentration-dependent manner. However, this MAb did not have any effect on tumor-cell adhesion and migration to the extracellular matrices, which may be involved in tumor-cell invasion. MAb WM15 inhibited the degradation of type-IV collagen by tumor cells in a concentration-dependent manner. We also found that WM15 inhibited hydrolysing activities towards substrates of aminopeptidases in 3 different tumor cells. Since our previous study indicated that bestatin, an aminopeptidase inhibitor, was able to inhibit tumor-cell invasion, as well as aminopeptidase activities of murine and human metastatic tumor cells, cell-surface amino-peptidase N/CD13 may be partly involved in the activation mechanism for type-IV collagenolysis to achieve tumor-cell invasion, and anti-CD13 MAb WM15 may inhibit tumor-cell invasion through a mechanism involving its inhibitory action on the aminopeptidase N in tumor cells.

Dynamic multichannel near-infrared optical imaging of human brain activity

Abstract: The present paper demonstrates functional brain mapping with an optical imaging technique by using tissue-transparent near-infrared light. With a maximal five-channel optical monitoring system, we succeeded in detecting region-specific changes in both the hemoglobin oxygenation state and blood volume during various mental tasks, in addition to visual and auditory stimulation. The time course of increases in blood supply varied with each brain region and depended on the type of internal operations occurring during the mental tasks. Changes in the hemoglobin oxygenation state were also different from region to region. This showed that there were regional variations of the oxygen delivery-oxygen utilization relationship during activation of brain activity. The usefulness of multichannel near-infrared functional imaging was well documented.

NK1.1+ CD4+ CD8- thymocytes with specific lymphokine secretion.

Abstract: CD4+8- or CD4-8+ thymocytes have been regarded as direct progenitors of peripheral T cells. However, recently, we have found a novel NK1.1+ subpopulation with skewed T cell antigen receptor (TcR) V beta family among heat-stable antigen negative (HSA-) CD4+8- thymocytes. In the present study, we show that these NK1.1+ CD4+8- thymocytes, which represent a different lineage from the major NK1.1- CD4+8- thymocytes or CD4+ lymph node T cells, vigorously secrete interleukin (IL)-4 and interferon (IFN)-gamma upon stimulation with immobilized anti-TcR-alpha beta antibody. On the other hand, neither NK1.1- CD4+8- thymocytes nor CD4+ lymph node T cells produced substantial amounts of these lymphokines. A similar pattern of lymphokine secretion was observed with the NK1.1+ CD4+T cells obtained from bone marrow. The present findings elucidate the recent observations that HSA- CD4+8- thymocytes secrete a variety of lymphokines including IFN-gamma, IL-4, IL-5 and IL-10 before the CD4+8- thymocytes are exported from thymus. Our evidence indicates that NK1.1+ CD4+8- thymocytes are totally responsible for the specific lymphokine secretions observed in the HSA- CD4+8- thymocytes.

Gene structure of CYP3A4, an adult-specific form of cytochrome P450 in human livers, and its transcriptional control.

Abstract: CYP3A4 is the adult-specific form of cytochrome P450 in human livers [Komori, M., Nishio, K., Kitada, M., Shiramatsu, K., Muroya, K., Soma, M., Nagashima, K. & Kamataki, T. (1990) Biochemistry 29, 4430–4433]. The sequences of three genomic clones for CYP3A4 were analyzed for all exons, exon-intron junctions and the 5′-flanking region from the major transcription site to nucleotide position -1105, and compared with those of the CYP3A7 gene, a fetal-specific form of cytochrome P450 in humans. The results showed that the identity of 5′-flanking sequences between CYP3A4 and CYP3A7 genes was 91%, and that each 5′-flanking region had characteristic sequences termed as NFSE (P450NF-specific element) and HFLaSE (P450HFLa specific element), respectively. A basic transcription element (BTE) also lay in the 5′-flanking region of the CYP3A4 gene as seen in many CYP genes [Yanagida, A., Sogawa, K., Yasumoto, K. & Fujii-Kuriyama, Y. (1990) Mol. Cell. Biol. 10, 1470–1475]. The BTE binding factor (BTEB) was present in both adult and fetal human livers. To examine the transcriptional activity of the CYP3A4 gene, DNA fragments in the 5′-flanking region of the gene were inserted in front of the simian virus 40 promoter and the chloramphenicol acetyltransferase structural gene, and the constructs were transfected in HepG2 cells. The analysis of the chloramphenicol acetyltransferase activity indicated that (a) specific element(s) which could bind with a factor(s) in livers was present in the 5′-flanking region of the CYP3A4 gene to show the transcriptional activity.

Secretion of acid phosphatase by the roots of crop plants under phosphorus-deficient conditions and some properties of the enzyme secreted by lupin roots

Abstract: Nine crop species were grown in P-sufficient and P-deficient nutrient solutions. The activity of acid phosphatase secreted by the roots increased under P-deficient conditions in all the species examined. That of lupin increased most remarkably. The properties of the enzyme secreted by the roots of lupin was investigated. Many isozymes existed in the roots and the leaves, but only one of them was secreted into the rhizosphere in a large amount. The molecular weight of the purified enzyme secreted was estimated to be 72 KD by SDS-PAGE and 140 KD by gel filtration; it was assumed to be a homo-dimer. The iso-electric point of the enzyme was 4.7 and the pH for optimum activity 4.3. When the enzyme was mixed with aqueous solution extracted from a P-deficient soil, its activity declined to 55% of its original activity after 14 days and to 9% after 21 days.

Birth of Mice after Transplantation of Early Cell-Cycle-Stage Embryonic Nuclei into Enucleated Oocytes

Abstract: The present study was conducted to investigate the influence of cell cycle stage of the donor nucleus on chromatin structure and development of mouse embryonic nuclei transplanted into enucleated oocytes. Donor cell-cycle stage was controlled in order to examine, in addition, the developmental potential of nuclei from 2-, 4-, and 8-cell-stage embryos. The cell cycle stage of donor nuclei was classified as early, middle, or late. After nuclear transfer, electrofusion, and activation, early-stage transplants formed a single pronucleus-like structure, but middle-stage transplants formed very irregular types of structures and ate-stage transplants extruded a polar body. A high proportion of development to the blastocyst stage (77.8%) and an increased cell number (62.1 cells) were obtained from the early 2-cell-stage transplants as opposed to the middle- (0% ) and late-stage (20.8%, 37.0 cells) transplants (p < 0.001). With transplantation of early-stage nuclei, high proportions of development to the blastocyst stage and of offspring were obtained from nuclear transplant embryos with a nucleus from a 2-, 4-, or 8-cell-stage embryo. The results confirm that the donor cell-cycle stage critically affects the chromatin structure and development of nuclear transplant embryos. The results also demonstrate that the nuclei from 2-, 4-, and 8-cell-stage mouse embryos in the early stage of each cell cycle can be reprogrammed when transplanted into enucleated mature oocytes.

Experimental approaches on measuring the mechanical properties and constitutive laws of arterial walls.

Abstract: Studies on the elastic properties of arterial walls which have been done for the past two decades are surveyed briefly. After several in vitro and in vivo experimental methods and clinical techniques for the measurements of the mechanical behavior of arterial walls have been reviewed, data obtained of the basic characteristics of the arterial wall, including wall incompressibility and anisotropy, are discussed. The author then reviews constitutive laws proposed for the description of stress-strain relationships of arterial walls and methods for the parametric expression of pressure-diameter data, and shows data on the effects of aging and vascular diseases on arterial mechanics. Finally, residual stress in the arterial wall is discussed.

Acute brain swelling after out-of-hospital cardiac arrest: pathogenesis and outcome.

Abstract: Objectives First, to examine factors that may be related to brain swelling, which was identified by the absence or compression of the lateral and third ventricles and perimesencephalic cisterns on brain computed tomography (CT) scans in the early postresuscitation period in patients who suffered an out-of-hospital cardiac arrest. Second, to characterize the neurologic outcome in those patients in whom cardiac arrest was followed by brain swelling. Design Prospective and retrospective analyses. Settings General ICU, tertiary care hospital. Patients Fifty-three patients (35 male, 18 female) who had an out-of-hospital cardiac arrest and who also had a brain CT examination on the third day after resuscitation. The 53 patients were divided into two groups: group A (25 patients) experienced brain swelling on postresuscitation day 3; group B (28 patients) did not experience noticeable brain swelling. Interventions None Measurements and Main Results There was a significant difference between the two groups in the etiology of the cardiac arrest. Twenty-three of 25 patients in group A had cardiac arrest due to respiratory distress, whereas this finding was true in only five patients in group B. In laboratory data, arterial pH was significantly lower in group A than in group B (6.93 vs. 7.09), as was base deficit (-21.0 mmol/L in group A vs. −13.7 mmol/L in group B). Neurologic outcome was evaluated 1 wk after resuscitation. There were significantly more patients in group A who were not awake and who were diagnosed as braing dead. Conclusions The cause of brain swelling may be related to the development of the metabolis acidosis (possibly lactic acidosis) due to hypoxie before the resuscitation period. Brain swelling may be one of the indicators that predicts a poes neurologic outcome in the patients who suffes an out-of-hospital cardiac arrest. (Crit Care Med 1993; 21:104–110)

Highly selective supported Pd catalysts for steam reforming of methanol

Abstract: Steam reforming of methanol, CH3OH + H2O → 3H2 + CO2, was carried out over various Pd catalysts (Pd/SiO2, Pd/Al2O3, Pd/La2O3, Pd/Nb2O5, Pd/Nd2O3, Pd/ZrO2, Pd/ZnO and unsupported Pd). The reaction was greatly affected by the kind of support. The selectivity for the steam reforming was anomalously high over Pd/ZnO catalysts.

Effects of exposure to a circularly polarized 50-Hz magnetic field on plasma and pineal melatonin levels in rats.

Abstract: We sought to determine whether a 6-week exposure to a 50-Hz rotating magnetic field influences melatonin synthesis by 11-18 week-old Wistar-King male rats. Rats were exposed continuously to a rotating magnetic field at 1, 5, 50, or 250 microT (spatial vector rms) for 6 weeks, except for twice-weekly breaks of about 2 h for cleaning of cages and feeding. The rats were housed in exposure and sham-exposure facilities, which were located in the same room, under a 12:12 light-dark photoperiod (lights on at 06:00 h). The room was constantly illuminated by 4 small, dim red lights (< 0.07 lux in dark period). Levels of plasma and pineal gland melatonin were determined by radioimmunoassay. A significant decrease of melatonin was observed between the control group and groups exposed to a magnetic field at a flux density in excess of 1 microT during the night time, but no statistical differences were found among the exposed groups. These results indicate that subchronic exposure of albino rats to a 50-Hz rotating magnetic field influences melatonin production and secretion by the pineal gland.

Correlation between histopathologic features and magnetic resonance images of spinal cord lesions.

Abstract: The authors report a correlation between histopathologic features and magnetic resonance images of spinal cord lesions in 19 human spinal cords with various types of lesions. Abnormally high T2-weighted image signal intensities appeared nonspecifically in mildly altered lesions or areas with edema. In the gray matter, a low T1-weighted image in addition to a high T2-weighted image signal intensity appeared in severely altered lesions with necrosis, myelomalacia, or spongiform change. In the white matter, abnormally high T1-weighted image intensities appeared in severely altered lesions. Based on these preliminary results, it appears that a correlation between the degree of histopathologic alteration of the spinal cord and magnetic resonance images in clinical cases can be made. This is the first study to clarify the correlation between histopathologic features and magnetic resonance images of the diseased human spinal cord.

Swelling of poly(N-isopropylacrylamide) gels in water-alcohol (C1-C4) mixed solvents

Abstract: The swelling volume of poly(N-isopropylacrylamide) gels in alcohol-water mixtures (C 1 -C 4 ) was measured at 25 o C. The swollen gel in water shrank first with addition of a small amount of alcohol and then reswelled on further addition of alcohol showing a typical reentrant transition. The swelling behavior of the gels was correlated with the properties of the aqueous alcohol mixtures (i.e., the change of alcohol molar volume and thermodynamic activities of alcohol and water). The uptake of ethanol and water in the equilibrated gels was measured at 25 o C. Ethanol was found to be selectively taken up in all aqueous alcohol mixtures

Acetazolamide test in detecting reduced cerebral perfusion reserve and predicting long-term prognosis in patients with internal carotid artery occlusion.

Abstract: In a series of 32 patients with internal carotid artery occlusion, regional cerebral blood flow (rCBF) and regional cerebral vasoreactivity (rCVR) were measured by xenon-133 single photon emission computed tomography and the acetazolamide test. We evaluated its usefulness in detecting the reduced cerebral perfusion reserve and predicting long-term prognosis. All Type 1 patients (normal rCBF and rCVR) were medically treated and experienced no recurrent ischemic attack. Cerebral hemodynamics remained unchanged. Type 2, 3, and 4 patients underwent superficial temporal artery-middle cerebral artery double anastomosis, if they consented to surgery. All Type 2 (normal rCBF and reduced rCVR) and Type 3 (reduced rCBF and rCVR) patients, who underwent surgery, showed no further ischemic attacks, as well as long-term normalization of rCVR, although long-term rCBF normalization was obtained in only three of seven Type 3 patients. Cerebral hemodynamics remained unchanged in Type 4 patients after surgery. In follow-up periods, major completed stroke occurred in all 3 Type 2 and Type 3 patients who were medically treated. These results suggest that the acetazolamide test is valuable in assessing the cerebral perfusion reserve and predicting long-term prognosis in patients with internal carotid artery occlusion, although further long-term or randomized studies are needed.

Effects of stress shielding on the mechanical properties of rabbit patellar tendon

Abstract: Mechanical properties of the stress-shielded patellar tendon were studied in the rabbit knee. Stress shielding was accomplished by stretching a stainless-steel wire installed between the patella and tibial tubercle and thus, releasing the tension in the patellar tendon completely. Tensile tests were carried out on the specimens obtained from the patellar tendons which were exposed to the stress shielding for 1 to 6 weeks. The stress shielding changed the mechanical properties of the patellar tendon significantly: it decreased the tangent modulus and tensile strength to 9 percent of the control values after 3 weeks. There was a 131 percent increase in the cross-sectional area and a 15 percent decrease in the tendinous length. Remarkable changes were also observed in the structural properties: for example, the maximum load of the bone-tendon complex decreased to 20 percent of the control value after 3 weeks. Histological studies showed that the stress shielding increased the number of fibroblasts and decreased the longitudinally aligned collagen bundles. These results imply that if no stress is applied to the autograft in the case of augmentative reconstruction of the knee ligament, the graft strength decreases remarkably.

Chromosome condensation in Xenopus mitotic extracts without histone H1

Abstract: The contribution of histone H1 to mitotic chromosome condensation was examined with the use of a cell-free extract from Xenopus eggs, which transforms condensed sperm nuclei into metaphase chromosomes. When H1 was removed from the extract, the resultant metaphase chromosomes were indistinguishable from those formed in complete extract. Nucleosomal spacing was the same for both. Thus, H1 is not required for the structural reorganization that leads to condensed metaphase chromosomes in this egg extract.

Oxidative Stability of Polyunsaturated Fatty Acids in an Aqueous Solution

Abstract: The relative oxidative stability of six kinds of typical polyunsaturated fatty acids (PUFAs) was investigated in an aqueous solution (pH=7.4 at 37°C) with Fe2+-ascorbic acid as a catalyst. The highest stability was shown by docosahexaenoic acid (22: 6n-3, DHA), followed by eicosapentaenoic (20: 5n-3), arachidonic (20: 4n-6), α-linolenic (18: 3n-3), γ-linolenic (18: 3n-6), and linoleic (18: 2n-6, LA) acids, indicating that the stability increased with increasing degree of unsaturation. The significant difference found between α-linolenic and γ-linolenic acids also suggests the higher oxidative stability of n-3 PUFAs than of n-6 PUFAs in an aqueous solution. Moreover, when a mixture of DHA and LA was oxidized in an aqueous solution, the stability increased with increasing molar ratio of DHA to LA in the mixture. This characteristic oxidative stability of PUFAs in the aqueous phase is quite different from that in the neat phase, and can be explained by correlating with the conformation of PUFAs in the aqueou...

Anaerobic waste-activated sludge digestion - A bioconversion mechanism and kinetic model

Abstract: The anaerobic bioconversion of raw and mechanically lysed waste-activated sludge was kinetically investigated. The hydrolysis of the biopolymers, such as protein, which leaked out from the biological sludge with ultrasonic lysis, was a first-order reaction in anaerobic digestion and the rate constant was much higher that the decay rate constant of the raw waste activated sludge. An anaerobic digestion model that is capable of evaluating the effect of the mechanical sludge lysis on digestive performance was developed. The present model includes four major biological processes-the release of intracellular matter with sludge lysis; hydrolysis of biopolymers to volatile acids; the degradation of various volatile acids to acetate; and the conversion of acetate and hydrogen to methane. Each process was assumed to follow first order kinetics. The model suggested that when the lysed waste-activated sludge was fed, the overall digestive performance remarkably increased in the two-phase system consisting of an acid forming process and a methanogenic process, which ensured the symbiotic growth of acetogenic and methanogenic bacteria.

Immunochemical detection of advanced glycation end products in lens crystallins from streptozocin-induced diabetic rat

Abstract: To reassess the significance of AGEs in cataract formation in diabetic animals, we measured amounts of AGEs in lens crystallins from STZ-induced diabetic animals with a newly developed ELISA. Lenses were removed at 5 and 20 wk after STZ injection. In 20-wk diabetic rats, all lenses were cataractous but not in control rats. In 20-wk diabetic compared with control rats, significant increases were observed in AGEs (172.3 +/- 18.3 vs. 14.3 +/- 1.7 AU, P 12-fold higher in diabetic rats. In agreement with earlier studies, we found that fluorescence in lens crystallins increased by 61% in diabetic rats. In 5-wk diabetic rats, all lenses were noncataractous. In 5-wk diabetic compared with control rats, significant increases were observed in AGEs (84.1 +/- 7.7 vs. 9.4 +/- 1.5 AU, P < 0.01) and fluorescence (1.45 +/- 0.06 vs. 1.05 +/- 0.06 AU, P < 0.01). Analysis of the AGE content by ELISA showed that accumulation of AGEs in diabetic lens crystallins does markedly occur with time, and a large amount of AGEs exists in the diabetic (cataractous) lens crystallins. The disproportionate elevation of AGEs, measured by the ELISA, compared with fluorescence suggests that the actual levels of AGEs in cataractous lens crystallins from diabetic animals are higher than previously anticipated, and nonfluorescent AGEs may exist in diabetic lens crystallins.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of MS‐551, a new class III antiarrhythmic drug, on action potential and membrane currents in rabbit ventricular myocytes

Abstract: 1. Electrophysiological effects of MS-551, a new class III antiarrhythmic drug, were examined and compared with those of (+)-sotalol in rabbit ventricular cells. 2. In rabbit ventricular muscles stimulated at 1.0 Hz, MS-551 (0.1-10 microM) and (+)-sotalol (3-100 microM) prolonged action potential duration (APD) and effective refractory period without affecting the maximum upstroke velocity of phase 0 depolarization (Vmax). The class III effect of MS-551 was approximately 30 times more potent than that of (+)-sotalol. 3. Class III effects of MS-551 and (+)-sotalol showed reverse use-dependence, i.e., a greater prolongation of APD at a longer cycle length. 4. In rabbit isolated ventricular cells, 3 microM MS-551 and 100 microM sotalol inhibited the delayed rectifier potassium current (IK) which was activated at more positive potentials than -50 mV and saturated around +20 mV. 5. MS-551 at a higher concentration of 10 microM decreased the transient outward current (Ito) and the inward rectifier potassium current (IK1) although 100 microM sotalol failed to inhibit these currents. 6. MS-551 is a non-specific class III drug which can inhibit three voltage-gated K+ channels in rabbit ventricular cells.