Search PubMed⌕ Search

Biomedical subjects

C Kondo

Publications and source records attributed to C Kondo.

At least 37 records · Page 2Linked to original sources
PubMed1998

Chimeras of Kir6.1 and Kir6.2 reveal structural elements involved in spontaneous opening and unitary conductance of the ATP-sensitive K+ channels.

The ATP-sensitive K+ (KATP) channels, e.g. in heart and pancreatic beta-cells, open spontaneously in the absence of intracellular ATP (ATPi). Their unitary conductance is approximately 80 pS with 150 mM extracellular K+. These features are shared by the K+ channels composed of various sulfonylurea receptors (SURs) and Kir6.2, whereas SUR/Kir6.1 channels have a smaller conductance (approximately 35 pS) and do not open spontaneously in the absence of ATPi. To identify the structural elements in Kir6.0 subunits which determine these properties, we analyzed the properties of functional K+ channels composed of SUR2A, the cardiac type SUR, and various chimeras of Kir6.1 and Kir6.2 heterologously expressed in HEK (human embryonic kidney) 293T cells. The analyses indicate that the extracellular linker domain between the two putative membrane-spanning regions is responsible for the difference in the single channel conductance between SUR2A/Kir6.1 and SUR2A/Kir6.2 channels. The cytosolic N-terminal domain of Kir6.2 was mandatory for spontaneous channel opening in the absence of ATPi, although a part of C-terminus was also involved. These results implicate specific regions of Kir6.0 in the spontaneous opening and the single channel conductance.

Adenosine Triphosphate↗
PubMed1997

Sulphonylurea receptor 2B and Kir6.1 form a sulphonylurea-sensitive but ATP-insensitive K+ channel.

1. We analysed the K+ channel composed of the sulphonylurea receptor 2B (SUR2B) and an inwardly rectifying K+ channel subunit Kir6.1 coexpressed in a mammalian cell line, HEK293T, with the patch clamp technique. 2. In the cell-attached configuration, K+ channel openers (pinacidil and nicorandil) activated approximately 33 pS K+ channels (approximately 145 mM external K+), which were inhibited by the sulphonylurea glibenclamide. 3. Although SUR2B forms an ATP-sensitive K+ channel with Kir6.2, whose amino acid sequence is approximately 70% homologous with that of Kir6.1, the K+ channel composed of SUR2B and Kir6.1 surprisingly did not spontaneously open on patch excision in the absence of intracellular ATP. 4. In inside-out patches, uridine diphosphate and guanosine diphosphate induced channel activity, which was inhibited by glibenclamide but not ATP. Intracellular ATP on its own activated the channels. K+ channel openers and intracellular nucleotides synergistically activated the channel. 5. Therefore, the K+ channel composed of SUR2B and Kir6.1 is not a classical ATP-sensitive K+ channel but closely resembles the nucleotide diphosphate-dependent K+ channel in vascular smooth muscle cells.

ATP-Binding Cassette Transporters↗
PubMed1997

Small left coronary arteries after arterial switch operation for complete transposition.

BACKGROUND: Myocardial perfusion is not completely normal and ventricular function is depressed in some patients after the arterial switch operation. The basic mechanism has not yet been defined totally. METHODS: The diameters of the right, left main trunk, anterior descending, and circumflex coronary arteries were measured by computer-assisted densitometry at 8 to 86 months (mean, 47.5 months) after the arterial switch operation in 86 patients. RESULTS: The Z scores, compared with control, were +2.0 +/- 0.3, -1.8 +/- 0.3, and -1.5 +/- 0.3 for the right, left anterior descending, and circumflex coronary arteries, respectively. The Z score for the total cross-sectional area of the three vessels was -1.5 +/- 0.3. These parameters did not correlate with left ventricular ejection fraction. CONCLUSIONS: At the midterm follow-up after the arterial switch operation for complete transposition of the great arteries, the left coronary arteries are small. A careful follow-up study is mandatory to clarify the clinical significance of this finding.

Absorptiometry, Photon↗
PubMed1997

Electrophysiological characterization of an alternatively processed ERG K+ channel in mouse and human hearts.

Mutants of HERG, the human form of ERG (the ether-a-go-go-related K+ channel gene), are responsible for some forms of the long-QT syndrome, an abnormality of cardiac repolarization. HERG was cloned from brain and has properties similar but not identical to the rapidly activating component of the native cardiac K+ channel current (Ikr). We identified in the mouse an alternatively processed form of ERG (MERG B) that is expressed abundantly in heart but only in trace amounts in brain. MERG B has a unique 36-amino acid NH2-terminal domain that is strongly basic and considerably shorter than the 376-amino acid NH2-terminal domain of HERG. When expressed in Xenopus oocytes, the kinetics of activation and deactivation of the MERG B current were best fit by a biexponential function, with the fast components dominant over the slow components. The fast component of activation had a mean tau value of 163 +/- 16 ms at -20 mV and 8 +/- 4 ms at +20 mV (n = 4). The fast component of deactivation had a mean tau value of 145 +/- 29 ms at -20 mV and 12 +/- 4 ms at -90 mV (n = 4). The MERG B current was blocked by the selective IKr blocker, dofetilide, with an IC50 of 54 nmol/L. In addition, we isolated HERG B, the human homologue of MERG B, which has electrophysiological characteristics qualitatively similar to those of MERG B. We have identified ERG B, an alternatively processed isoform of the ERG gene, expressed selectively in heart and with electrophysiological characteristics similar to those of native cardiac IKr.

Amino Acid Sequence↗
PubMed1997

Giant hepatic angiomyolipoma associated with disseminated intravascular coagulation.

We report a case of giant hepatic angiomyolipoma in a 68-year-old woman who had an increase in the fibrinolytic activity concomitant with disseminated intravascular coagulation (DIC). The presence of the tumor was confirmed by ultrasound (US), computed tomography (CT) and magnetic resonance imaging (MRI) of the abdomen and the selective arteriography of the liver via the superior mesenteric artery. Following treatment with heparin and gabexate mesilate, abnormal hemostatic values were corrected. Furthermore, the surgical removal of the huge hepatic angiomyolipoma completely normalized the alternations of the clotting system. These findings suggest that giant hepatic angiomyolipoma was profoundly associated with DIC.

Aged↗
PubMed1997

Inwardly rectifying potassium channels: their molecular heterogeneity and function.

A variety of cells including cardiac myocytes and neuronal cells possess inwardly rectifying K+ (Kir) channels through which currents flow more readily in the inward direction than outward. These K+ channels play pivotal roles in maintenance of the resting membrane potential, in regulation of the action potential duration, in receptor-dependent inhibition of cellular excitability, and in the secretion and absorption of K+ ions across cell membrane. Recent molecular biological dissection has shown that the DNAs encoding Kir channels constitute a new family of K+ channels whose subunits contain two putative transmembrane domains and a pore-forming region. So far, more than ten cDNAs of Kir channel subunits have been isolated and classified into four subfamilies: 1) IRK subfamily (IRK1-3/Kir1.1-1.3), 2) GIRK subfamily (GIRK1-4/Kir3.1-3.4), 3) ATP-dependent Kir subfamily (ROMK1/Kir1.1, K(AB)-2/Kir4.1), and 4) ATP-sensitive Kir subfamily (uKATP-1/Kir6.1, BIR/Kir6.2). Xenopus oocytes injected with the cRNAs of IRKs elicit classical Kir channel currents. GIRKs, as heteromultimers, compose the G protein-gated Kir (KG) channels, which are regulated by a variety of Gi/Go-coupled inhibitory neurotransmitter receptors such as m2-mus-carinic, serotonergic (5HT1A), GABAB, somatostatin and opioid (mu, delta, kappa) receptors. ROMK1 and KAB-2 are characterized with a Walker type-A ATP-binding motif in their carboxyl termini, and may be involved in K+ transport in renal epithelial and brain glial cells. uKATP-1 and BIR form with sulfonylurea receptors, the so-called ATP-sensitive K+ channels. Thus, it is a feature of the Kir channel family that each subfamily plays a specific physiological functional role. The (Na+)-activated Kir channels identified electrophysiologically in neurons and cardiac myocytes have not yet been cloned. In this review, we overviewed the current understandings of the features of the molecular structures and functions of the four main subfamilies of Kir channels.

Amino Acid Sequence↗
PubMed1996

Cloning and functional expression of a novel isoform of ROMK inwardly rectifying ATP-dependent K+ channel, ROMK6 (Kir1.1f).

We have identified from rat kidney a novel isoform of ROMK/Kir1.1, designated ROMK6/Kir1.1f. ROMK6 was nearly identical to ROMK1, but possessed an 122-bp insertion in the 5' region. Its deduced amino acid sequence was shorter by 19 amino acids than that of ROMK1 in the amino-terminus. Unlike other previously reported ROMK isoforms, ROMK6 mRNA was ubiquitously expressed in various tissues, including kidney, brain, heart, liver, pancreas and skeletal muscle. Xenopus oocytes injected with ROMK6 cRNA expressed a Ba2+-sensitive weakly inwardly rectifying K+ current. These results indicate that ROMK6 is a novel functional K+ channel and might be involved in K+ secretion in various tissue.

Adenosine Triphosphate↗
PubMed1996

A novel sulfonylurea receptor forms with BIR (Kir6.2) a smooth muscle type ATP-sensitive K+ channel.

We have isolated a cDNA encoding a novel isoform of the sulfonylurea receptor from a mouse heart cDNA library. Coexpression of this isoform and BIR (Kir6.2) in a mammalian cell line elicited ATP-sensitive K+ (KATP) channel currents. The channel was effectively activated by both diazoxide and pinacidil, which is the feature of smooth muscle KATP channels. Sequence analysis indicated that this clone is a variant of cardiac type sulfonylurea receptor (SUR2). The 42 amino acid residues located in the carboxyl-terminal end of this novel sulfonylurea receptor is, however, divergent from that of SUR2 but highly homologous to that of the pancreatic one (SUR1). Therefore, this short part of the carboxyl terminus may be important for diazoxide activation of KATP channels. The reverse transcription-polymerase chain reaction analysis showed that mRNA of this clone was ubiquitously expressed in diverse tissues, including brain, heart, liver, urinary bladder, and skeletal muscle. These results suggest that this novel isoform of sulfonylurea receptor is a subunit reconstituting the smooth muscle KATP channel.

ATP-Binding Cassette Transporters↗
PubMed1996

Cardiac anomalies associated with a chromosome 22q11 deletion in patients with conotruncal anomaly face syndrome.

Among 114 cardiac patients with conotruncal anomaly face syndrome and DiGeorge syndrome, 100 patients were found to have a chromosome 22q11 deletion. Those with the deletion included 73 patients with tetralogy of Fallot, 12 with ventricular septal defect, 5 with aortic arch anomalies without intracardiac anomaly, 4 with interrupted aortic arch, 2 with double-outlet right ventricle, 2 with truncus arteriosus, 1 with complete transposition, and 1 with atrial septal defect.

Child, Preschool↗
PubMed1996

Competition between Mg2+ and spermine for a cloned IRK2 channel expressed in a human cell line.

1. A cloned inwardly rectifying K+ channel, IRK2, was expressed in a human cell line, human embryonic kidney (HEK) 293T. Its electrophysiological properties were examined using the patch clamp technique in the whole-cell, cell-attached and inside-out patch configurations. 2. The cells transfected with IRK2 cDNA exhibited a K+ current which showed classical properties of inwardly rectifying K+ channels at both whole-cell and single-channel levels. 3. In the inside-out patch configuration, intracellular Mg2+ (Mg2+i blocked the outward currents in a voltage-dependent and virtually time-independent manner. Mg2+i (1-100 microM) caused a decrease in the unitary current amplitude of the IRK2 channel by inducing subconducting levels. 4. In the absence of Mg2+i, intracellular spermine blocked the outwardly flowing IRK2 currents in a voltage- and time-dependent manner. Spermine (1-100 nM) did not affect the unitary channel current amplitude but reduced the channel open probability. The spermine block showed a slower time and steeper voltage dependence than the Mg2+i++ block. 5. When both these blockers were present, Mg2+i apparently attenuated the inhibitory effect of spermine on the outwardly flowing IRK2 currents. This interaction was voltage and time dependent, and could be well explained by a model in which Mg2+i and spermine competitively bind to the channel with their individual first-order kinetics. This competition would induce time-dependent transits of the channel between the Mg2+i -and spermine-blocked states via a single open state, thereby preserving a certain size of persistent outward currents at depolarized potentials.

Barium↗
PubMed1996

A novel ubiquitously distributed isoform of GIRK2 (GIRK2B) enhances GIRK1 expression of the G-protein-gated K+ current in Xenopus oocytes.

We have isolated a novel variant form of GIRK2, designated GIRK2B, from mouse brain cDNA library. GIRK2B was much shorter than the first type of GIRK2 (GIRK2A), but its amino acid sequence was identical to the corresponding part of GIRK2A except the C-terminal eight amino acid residues. When GIRK2B cRNA was co-injected with GIRK1 and m2-receptor cRNAs to Xenopus oocytes, acetylcholine-induction of the inwardly rectifying K+ current was enhanced dramatically. This suggests that GIRK2B can form a heteromultimeric G-protein-gated K+ channel with GIRK1. The reverse transcription polymerase chain reaction analysis showed that GIRK2B mRNA distributed much more broadly than GIRK1 mRNA. Therefore, GIRK2B might also play other unrecognized roles in various tissues than to form a K+ channel with GIRK1.

Amino Acid Sequence↗
PubMed1996

Growth hormone-secreting pituitary adenoma associated with multiple bone cysts, skin pigmentation and aortitis syndrome.

McCune-Albright syndrome (MAS) is clinically characterized by polyostotic fibrous dysplasia, cafe au lait pigmentation of the skin and multiple endocrinopathies. Recently activating mutations of codon 201 in the gene encoding Gs alpha have been found in affected tissues in MAS. Herein we report a case of acromegaly associated with multiple bone cysts and skin pigmentation in a 47-year-old women. She had suffered a history of aortitis syndrome. The DNA sequence indicated that a Cys201 for Arg201 substitution was found in the GH secreting pituitary adenoma tissue but not in peripheral mononuclear cells. We speculate that the patient has a possible variant from of MAS characterized by multiple bone lesions skin pigmentation and GH-secreting pituitary adenoma.

Adenoma↗
PubMed1996

Tetralogy of Fallot with pulmonary atresia associated with chromosome 22q11 deletion.

OBJECTIVES: The purpose of this study was to clarify characteristics of tetralogy of Fallot and pulmonary atresia associated with chromosome 22q11 deletion. BACKGROUND: DiGeorge syndrome and conotruncal anomaly facies syndrome are associated with chromosome 22q11 deletion (hemizygosity). Associated cardiac anomalies include tetralogy of Fallot, truncus arteriosus and interrupted aortic arch. METHODS: Twenty-three patients with tetralogy of Fallot and pulmonary atresia were proved to have chromosome 22q11 deletion with fluorescent in situ hybridization using N25 probe (Oncor). Cardiovascular anomalies were compared with those in 26 patients with tetralogy of Fallot and pulmonary atresia without the deletion. Cardiovascular anomalies were studied with cardiac catheterization, cineangiography and echocardiography. RESULTS: In patients with 22q11 deletion, additional anomalies of the aortic arch, ductus arteriosus and pulmonary artery were more common as follows: right aortic arch (70% with deletion vs. 23% without deletion), high aortic arch reaching third rib (43% vs. 15%), aberrant left subclavian artery (35% vs. 0%), absent ductus arteriosus (83% vs. 46%), major aortopulmonary collateral arteries (91% vs. 50%), absent confluent central pulmonary arteries (48% vs. 4%). CONCLUSIONS: In patients with tetralogy of Fallot and pulmonary atresia, additional anomalies of the aortic arch, ductus arteriosus and pulmonary arteries are more common in patients with than in those without the 22q11 deletion.

Abnormalities, Multiple↗
PubMed1995

Left ventricular dysfunction on exercise long-term after total repair of tetralogy of Fallot.

BACKGROUND: Excellent results regarding mortality are well recognized in the long-term period after intracardiac repair of tetralogy of Fallot. However, it is still unclear how postoperative sequelae affect cardiac performance during exercise. METHODS AND RESULTS: Twenty-nine patients with tetralogy of Fallot were studied 16 +/- 2 years after intracardiac repair by use of radionuclide first-pass ventriculography with an ultra-high-sensitive gamma camera at rest and at peak exercise on a semi-upright bicycle ergometer. The results were compared with those from 10 age- and sex-matched control subjects. Left and right ventricular ejection fraction and absolute ventricular volume were measured at rest and peak exercise. Regional right ventricular wall motion and diastolic function of the left ventricle were also assessed. Cardiac output of tetralogy was normally preserved both at rest and during exercise. Nevertheless, the incremental response of left ventricular ejection fraction during exercise was depressed in the patients. Left ventricular ejection fraction during exercise was inversely correlated with the right ventricular end-diastolic volume and the severity of pulmonary regurgitation. Regional wall motion at the right ventricular outflow tract was not decreased in the patients. Left ventricular diastolic function was not impaired in the patients compared with control subjects. CONCLUSIONS: Latent left ventricular dysfunction during exercise is related to an enlarged right ventricle due to pulmonary regurgitation after intracardiac repair of tetralogy. Careful follow-up is required in patients having significant pulmonary regurgitation.

Adult↗