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Biomedical subjects

G R Sutherland

Publications and source records attributed to G R Sutherland.

At least 91 records · Page 5Linked to original sources
PubMed2000

Normal regional right ventricular function and its change with age: a Doppler myocardial imaging study.

BACKGROUND: Doppler Myocardial Imaging (DMI) is a new technique currently being studied for the assessment of regional systolic and diastolic left ventricular (LV) function. No normal values or data on age-related changes in regional myocardial right ventricular (RV) velocities are available. METHODS AND RESULTS: Color DMI was used in 32 healthy volunteers (aged 16-76 years) to derive regional velocities from basal, medial, and apical segments of the RV free wall in the apical 4-chamber view, and from distal segments as well as from the tricuspid annulus in the parasternal long-axis view. Both mitral annular and regional LV velocities (4-chamber, long-axis parasternal view) were also recorded and compared with corresponding RV regional velocities. The M-mode displacement of the cardiac base was measured. Corresponding RV and LV DMI data sets were compared. For longitudinal function, RV free wall systolic velocities were consistently higher than velocities recorded in corresponding LV segments (analysis of variance, P <.05). Older subjects (40-76 years; 13 men, 2 women) had lower RV long-axis regional velocities than younger subjects (16-39 years; 15 men, 2 women), but had higher short-axis RV systolic velocities. For diastolic velocities, a negative correlation between age and the ratio of regional early diastolic to late diastolic velocity was shown for all RV free wall segments (eg, basal segment: r = -0.63, P <.0001). CONCLUSIONS: The right ventricle has higher long-axis regional velocities, a greater excursion of its lateral atrioventricular valve ring, and reduced circumferential shortening velocities compared with the left ventricle. Right ventricular longitudinal shortening is dominant over short-axis function in healthy young subjects. Normal age-related changes of diastolic velocities for each segment of the normal RV free wall have been defined.

Adolescent↗
PubMed2000

Are changes in myocardial integrated backscatter restricted to the ischemic zone in acute induced ischemia? An in vivo animal study.

Integrated backscatter (IB) from a myocardial region, calculated from radiofrequency echocardiographic data, has been proposed as a useful parameter for investigating changes in myocardial tissue induced by ischemia. In 10 closed-chest dogs, 5 minutes of myocardial ischemia was induced by either a proximal occlusion of the circumflex coronary artery (CX) (5 dogs), resulting in extensive ischemia in the posterior wall, or by occluding the distal CX vessel (5 dogs) to produce a small localized ischemic zone in the posterior wall. High-resolution digital radiofrequency data from the whole left ventricular myocardium, in the imaging plane during one complete heart cycle, were acquired with a whole-image real-time acquisition approach. Regions in the septum and posterior wall (both ischemic tissue and, in the case of distal occlusions, tissue surrounding the ischemic zone) were chosen for analysis, and IB and cyclic variation (CV) of IB were calculated. Post occlusion, an increase in mean IB values was found in the ischemic segment. However, an increase in CV was also observed in the peri-ischemic zone for the distal CX occlusion and in the septum after proximal CX occlusion. These findings show that changes in CV are not restricted to the ischemic zone but may also occur in distal myocardium. This may be explained by changes in the regional contractile state and loading conditions of the "normal" myocardium, which are altered in response to the distal ischemia.

Animals↗
PubMed2000

Assessment of regional longitudinal myocardial strain rate derived from doppler myocardial imaging indexes in normal and infarcted myocardium.

Myocardial deformation properties may be characterized by regional strain rates (SRs) calculated from Doppler myocardial velocity data. In 10 control subjects and 12 patients with established transmural infarcts, longitudinal median segmental SR, strain, and myocardial velocity were analyzed and compared with the corresponding wall motion score. All segments in control subjects and normal segments in infarct patients showed no significant difference in either systolic or diastolic SR (systolic: -1.27+/-0.39 s(-1) versus -1.23+/-0.24 s(-1), not significant [NS]; and isovolumic relaxation [IVR]: 1.23+/-0.38 s(-1) versus 1.95+/-0.62 s(-1), NS; respectively) and strain (-0.21+/-0.06 versus -0.19+/-0.06, NS). In infarcted segments, peak systolic SR, systolic strain, and early diastolic SR showed the most pronounced reduction (hypokinetic and akinetic) or even inversion (dyskinetic segments: 0.10+/-0.26 s(-1), 0.00+/-0.03, and -1.78+/-0.67 s(-1), respectively; P<.001). In this study, new myocardial deformation indexes were shown to quantitatively describe the function of normal and chronically infarcted regions.

Adult↗
PubMed2000

AR-R15896AR reduces cerebral infarction volumes after focal ischemia in cats.

OBJECTIVE: The use of competitive and noncompetitive N-methyl-D-aspartate receptor antagonists to prevent neuronal death during ischemia has been comprehensively studied. This study was performed to examine the neuroprotective effects and pharmacokinetics of the noncompetitive N-methyl-D-aspartate receptor channel blocker (S)-alpha-phenylpyridine-ethanamine dihydrochloride, AR-R15896AR (formerly designated ARL 15896AR), using a gyrencephalic cat middle cerebral artery occlusion model. METHODS: In a separate experiment, three cats were used for pharmacokinetic analysis, thus establishing the optimal dose of AR-R15896AR. Focal cerebral ischemia was induced in 21 cats. After 30 minutes of a 90-min ischemic insult, the cats received an intravenous infusion (total volume, 3 ml), in a 15-minute period, of either AR-R15896AR or normal saline solution (control). Physiological data were obtained after 40 and 80 minutes of ischemia and at 2, 4, and 6 hours after ischemia. At 6 hours after ischemia, each cat was positioned for both T2- and diffusion-weighted scans (eight slices, 5-mm thick). At 8 hours after ischemia, the animals were perfusion-fixed for histopathological analysis. RESULTS: Pharmacokinetic studies indicated that AR-R15896AR remained in the blood at elevated levels for the 6 hours studied, with a calculated half-life of approximately 6 hours. AR-R15896AR rapidly entered the brain and exhibited a brain/plasma ratio of approximately 8:1. The infarction volumes for the AR-R15896AR-treated group were 1138.5+/-363.1, 651.3+/-428.9, and 118.6+/-50.1 mm3, as calculated using diffusion- and T2-weighted MRI and histopathological data, respectively. The infarction volumes for the control group were 3866.3+/-921, 3536+/-995.7, and 359.9+/-80.2 mm3, as calculated using diffusion- and T2-weighted MRI and histopathological data, respectively. No significant changes were observed in the physiological parameters measured (mean arterial blood pressure, pH, arterial carbon dioxide pressure, arterial oxygen pressure, sodium, potassium, chloride, and glucose levels, hematocrit, and temperature) for either the control or AR-R15896AR-treated group. Postischemic calcium levels returned to normal in the AR-R15896AR-treated cats, whereas they decreased in the control cats. CONCLUSION: When administered after ischemia, AR-R15896AR was effective in significantly reducing infarction volumes, as measured using diffusion- or T2-weighted magnetic resonance imaging data or quantitative histopathological data. This study also demonstrated that infarction volumes were greater in the diffusion- and T2-weighted magnetic resonance imaging scans than in the qualitative histopathological analyses, with the diffusion-weighted scans exibiting the largest infarction volumes.

Animals↗
PubMed2000

Advances in mobile intraoperative magnetic resonance imaging.

OBJECTIVE: The goal was to enhance a mobile magnetic resonance imaging system developed for neurosurgery. Components of the system included an actively shielded, 1.5-T superconducting magnet, a titanium operating room table, a radiofrequency (RF) head coil that could be disassembled, and local RF shielding. METHODS: The system was designed and implemented by the Division of Neurosurgery, University of Calgary (Calgary, Alberta, Canada), in collaboration with the National Research Council of Canada Institute for Biodiagnostics (Winnipeg, Manitoba, Canada). The ceiling-mounted, 1.5-T magnet was moved into and out of the surgical field as required. After initial success in monitoring the resection of various intracranial and cranial base lesions, significant modifications to the system were made by Innovative Magnetic Resonance Imaging Systems, Inc. (Winnipeg, Manitoba, Canada), and BrainLAB (Heimstetten, Germany). These modifications included the design and construction of a shorter magnet with a larger bore and stronger gradients, widening of the titanium operating room table, modification of the RF coil housing to allow vertical movement and incorporation of a three-pin head-clamp, construction of a transparent, copper-impregnated RF shield, and integration with a surgical navigation system. RESULTS: The movable intraoperative imaging system has now been used for 101 neurosurgical procedures, including the previously reported cases. CONCLUSION: The modifications to the system have enhanced its integration with established neurosurgical techniques and have improved patient safety. The larger magnet bore size, together with the ability to move the RF coil vertically, allows placement of patients in prone or lateral positions. Surgical navigation has been successfully integrated with the intraoperatively acquired high-resolution images. The ability to identify and resect residual lesions before wound closure remains a tremendous immediate advantage of this technology.

Adolescent↗
PubMed2000

A de novo mutation in sporadic nocturnal frontal lobe epilepsy.

Autosomal dominant nocturnal frontal lobe epilepsy is sometimes due to mutations in CHRNA4. The commoner presentation of sporadic nocturnal frontal lobe epilepsy has not been associated with genetic defects. A 30-year-old woman diagnosed as having sporadic nocturnal frontal lobe epilepsy was found to have a de novo Ser252Leu CHRNA4 mutation. A pattern is emerging of site-specific mutation within the second transmembrane domain of CHRNA4 in association with autosomal dominant nocturnal frontal lobe epilepsy and sporadic nocturnal frontal lobe epilepsy in families with different ethnic backgrounds.

Adult↗
PubMed1999

Characterization of the human glutamate receptor subunit 3 gene (GRIA3), a candidate for bipolar disorder and nonspecific X-linked mental retardation.

The X-chromosome breakpoint in a female patient with a balanced translocation t(X;12)(q24;q15), bipolar affective disorder and mental retardation was mapped within the glutamate receptor 3 (GRIA3) gene by fluorescence in situ hybridization. The GRIA3 cDNA of 5894 bp was cloned, and the gene structure and pattern of expression were determined. The most abundant GRIA3 transcript is composed of 17 exons. An additional 5 exons (2a, 2b, 5a, 5b, and 5c) from the 5' end of the GRIA3 open reading frame were identified by EST analysis (ESTs AI379066 and AA947914). Two new polymorphic microsatellite repeats, (TC)(n=12-26) and (AC)(n=15-19), were identified within GRIA3 5' and 3'UTRs. No mutations were detected in families segregating disorders mapping across GRIA3, one with X-linked bipolar affective disorder (BP) and one with a nonspecific X-linked mental retardation (MRX27). To assess the possibility of the involvement of the GRIA3 gene in familial cases of complex BP, a large set of 373 individuals from 40 pedigrees segregating BP were genotyped using closely linked (DXS1001) and intragenic (DXS1212 and GRIA3 3' UTR (AC)(n))) GRIA3 STR markers. No evidence of linkage was found by parametric Lod score analysis (the highest Lod score was 0. 3 at DXS1212, using the dominant transmission model) or by affected sib-pair analysis.

Adult↗
PubMed1999

Molecular cloning and chromosomal mapping of the human homologue of MYB binding protein (P160) 1A (MYBBP1A) to 17p13.3.

We have previously isolated and characterized murine MYB binding protein (p160) 1a, a protein that specifically interacts with the leucine zipper motif within the negative regulatory domain of the c-Myb proto-oncoprotein. We now describe the molecular cloning of the human MYBBP1A cDNA and chromosomal localization to 17p13.3 by fluorescence in situ hybridization analysis. Given the likely presence of a tumor suppressor gene (or genes) within this region of chromosome 17, the position of MYBBP1A was further mapped by radiation hybrid analysis and was found to lie between markers D17S1828 and D17S938. A P1 artificial chromosome clone containing the 5' region of MYBBP1A was isolated and indicates a physical linkage between MYBBP1A and the 15-lipoxygenase gene (ALOX15). A novel, polymorphic (CA)(25) dinucleotide repeat was also isolated from this PAC and may serve as a useful marker for MYBBP1A and this region of chromosome 17.

Alleles↗
PubMed1999

Gamma-heregulin: a fusion gene of DOC-4 and neuregulin-1 derived from a chromosome translocation.

gamma-Heregulin was identified as an isoform resulting from alternate splicing of the neuregulin-1 gene, after cloning of its cDNA from the MDA-MB-175 breast cancer cell line. gamma-Heregulin was shown to promote growth of cultured MDA-MB-175 cells resulting from activation of its cognate ErbB tyrosine kinase reporters. We show here that gamma-heregulin is transcribed from a fusion gene resulting from a chromosome translocation in MDA-MB-175 cells. The fusion chromosome is described as dic(8:11)(8qter-->8p12::11q13-->11pter). As a result, the 5' end of the gamma-heregulin gene is derived from the stress-induced gene, DOC-4 (11q13), while the 3' end is from the neuregulin-1 gene (8p12). Thus, expression of gamma-heregulin is under the control of the DOC-4 promoter. By contrast with MDA-MB-175 cells, RT-PCR failed to detect a gamma-heregulin transcript in either E9.5 to E13.5 embryonic mouse tissues, adult mouse tissues or other human tumour cell lines. We conclude, therefore, that gamma-heregulin is not a native isoform of the neuregulin-1 gene, but a novel growth factor that may contribute to tumour cell proliferation.

Base Sequence↗
PubMed1999

Characterization and chromosomal localization of USP3, a novel human ubiquitin-specific protease.

Conjugation to the small eukaryotic protein ubiquitin can functionally modify or target proteins for degradation by the proteasome. Removal of the ubiquitin modification, or deubiquitination, is performed by ubiquitin-specific proteases and is an important mechanism regulating this pathway. Here we describe a novel human ubiquitin-specific protease, USP3, initially identified as a partial cDNA clone similar to one of two highly conserved sequence regions common to all ubiquitin-specific proteases. We have isolated a complete USP3 cDNA clone containing both of these conserved sequence regions. The USP3 gene appears to be single copy and maps to human chromosome 15q22.3. A USP3 probe detects two mRNA transcripts, one of which corresponds in length to the cDNA. Both are expressed at low levels in all tissues examined, with highest expression in pancreas. The USP3 protein is a functional ubiquitin-specific protease in vitro, and is able to inhibit ubiquitin-dependent degradation of both an N-end Rule substrate and abnormal endogenous proteins in yeast. USP3 is also only the second known ubiquitin-specific protease capable of efficiently cleaving a ubiquitin-proline bond.

Alternative Splicing↗
PubMed1999

Myeloid DAP12-associating lectin (MDL)-1 is a cell surface receptor involved in the activation of myeloid cells.

Crosslinking of immunoreceptor tyrosine-based activation motif (ITAM)-containing receptor complexes on a variety of cells leads to their activation through the sequential triggering of protein tyrosine kinases. Recently, DAP12 has been identified as an ITAM-bearing signaling molecule that is noncovalently associated with activating isoforms of MHC class I receptors on natural killer cells. In addition to natural killer cells, DAP12 is expressed in peripheral blood monocytes, macrophages, and dendritic cells, suggesting association with other receptors present in these cell types. In the present study, we report the molecular cloning of the myeloid DAP12-associating lectin-1 (MDL-1), a DAP12-associating membrane receptor expressed exclusively in monocytes and macrophages. MDL-1 is a type II transmembrane protein belonging to the C type lectin superfamily and contains a charged residue in the transmembrane region that enables it to pair with DAP12. Crosslinking of MDL-1/DAP12 complexes in J774 mouse macrophage cells resulted in calcium mobilization. These findings suggest that signaling via MDL-1/DAP12 complexes may constitute a significant activation pathway in myeloid cells.

Adaptor Proteins, Signal Transducing↗
PubMed1999

Two novel mucin genes down-regulated in colorectal cancer identified by differential display.

Epithelial mucins are large, secreted and cell surface glycoproteins involved in epithelial cell protection, adhesion modulation, and signaling. Using differential display, we have identified two novel mucin cDNAs (dd34 and dd29), hereafter designated MUC11 and MUC12, respectively, that are down-regulated in colorectal cancers. Northern blots demonstrated polydisperse signals characteristic of mucin transcripts in RNA from normal colon that were absent in colorectal cancer. Both cDNAs were mapped by fluorescence in situ hybridization to chromosome band 7q22, the location of the MUC3 mucin gene, thus suggesting that there may be a cluster of mucin genes at this locus. The sequences of both differential display clones were extended by a combination of screening libraries and PCR. The 2.8-kb MUC11 cDNA composite encoded 35 serine/threonine-rich, mucin-like degenerate 28 amino acid tandem repeats. The MUC12 cDNA composite encoded a putative transmembrane mucin containing two extracellular cysteine-rich, EGF-like domains, a coiled-coil region, and a mucin-like domain consisting of 28 amino acid degenerate tandem repeats. Distinct patterns of expression of MUC11, MUC12, and MUC3 mRNAs were observed in a range of normal human tissues. MUC12 mRNA was not expressed in any of six colorectal cancer cell lines examined and was down-regulated or absent in 6 of 15 (40%) tumors compared with matched normal colonic tissue. In contrast, MUC11 showed a different pattern of mRNA expression, with four of these lines showing low levels and the other two lines showing relatively high levels of MUC11 transcripts. Expression of MUC11 was down-regulated in the tumors of 12 of 15 (80%) paired samples. Structural homology of MUC12 with rat, mouse, and human MUC3 and human and rat MUC4/ASGP2 indicate that there is a distinct subfamily of transmembrane mucins with conserved epidermal growth factor domains. The homology of MUC12 with epidermal growth factor-like growth factors and its down-regulation in colorectal cancers, together with known interactions between rat MUC4 and c-erbB-2 growth factor receptors, suggests that MUC12 may be involved in epithelial cell growth regulation.

Amino Acid Sequence↗
PubMed1999

Identification, functional characterization, and chromosomal localization of USP15, a novel human ubiquitin-specific protease related to the UNP oncoprotein, and a systematic nomenclature for human ubiquitin-specific proteases.

We have identified a novel gene, USP15, encoding a human ubiquitin-specific protease (USP). The USP15 protein consists of 952 amino acids with a predicted molecular mass of 109.2 kDa and contains the highly conserved Cys and His boxes present in all members of the UBP family of deubiquitinating enzymes. USP15 shares 60.5% sequence identity and 76% sequence similarity with the human homolog (UNP/Unph/USP4) of the mouse Unp proto-oncogene. Recombinant USP15 demonstrated ubiquitin-specific protease activity against engineered linear fusions of ubiquitin to beta-galactosidase and glutathione S-transferase. USP15 can also cleave the ubiquitin-proline bond, a property previously unique to Unp/UNP. Chromosomal mapping by fluorescence in situ hybridization and radiation hybrid analyses localized the USP15 gene to chromosome band 12q14, a different location than that of UNP (3p21.3). Analysis of expressed sequence tag databases reveals evidence of alternate polyadenylation sites in the USP15 gene and also indicates that the gene may possess an exon/intron structure similar to that of the Unp gene, suggesting they have descended from a common ancestor. A systematic nomenclature for the human USPs is proposed.

Amino Acid Sequence↗
PubMed1999

Testisin, a new human serine proteinase expressed by premeiotic testicular germ cells and lost in testicular germ cell tumors.

We have cloned and characterized a cDNA encoding a new human serine proteinase, testisin, that is abundantly expressed only in the testis and is lost in testicular tumors. The testisin cDNA was identified by homology cloning using degenerate primers directed at conserved sequence motifs within the catalytic regions of serine proteinases. It is 1073 nucleotides long, including 942 nucleotides of open reading frame and a 113-nucleotide 3' untranslated sequence. Northern and dot blot analyses of RNA from a range of normal human tissues revealed a 1.4-kb mRNA species that was present only in testis, which was not detected in eight of eight testicular tumors. Testisin cDNA is predicted to encode a protein of 314 amino acids, which consists of a 19-amino acid (aa) signal peptide, a 22-aa proregion, and a 273-aa catalytic domain, including a unique 17-aa COOH-terminal hydrophobic extension that is predicted to function as a membrane anchor. The deduced amino acid sequence of testisin shows 44% identity to prostasin and contains features that are typical of serine proteinases with trypsin-like substrate specificity. Antipeptide antibodies directed against the testisin polypeptide detected an immunoreactive testisin protein of Mr 35,000-39,000 in cell lysates from COS-7 cells that were transiently transfected with testisin cDNA. Immunostaining of normal testicular tissue showed that testisin was expressed in the cytoplasm and on the plasma membrane of premeiotic germ cells. No staining was detected in eight of eight germ cell-derived testicular tumors. In addition, the testisin gene was localized by fluorescence in situ hybridization to the short arm of human chromosome 16 (16p13.3), a region that has been associated with allellic imbalance and loss of heterozygosity in sporadic testicular tumors. These findings demonstrate a new cell surface serine proteinase, loss of which may have a direct or indirect role in the progression of testicular tumors of germ cell origin.

Adult↗
PubMed1999

Cutting edge: human 2B4, an activating NK cell receptor, recruits the protein tyrosine phosphatase SHP-2 and the adaptor signaling protein SAP.

The genetic defect in X-linked lymphoproliferative syndrome (XLP) is the Src homology 2 domain-containing protein SAP. SAP constitutively associates with the cell surface molecule, signaling lymphocytic activation molecule (SLAM), and competes with SH2-domain containing protein tyrosine phosphatase-2 (SHP-2) for recruitment to SLAM. SLAM exhibits homology with the mouse cell surface receptor 2B4. The human homologue of 2B4 has now been identified. It is recognized by the c1.7 mAb, a mAb capable of activating human NK cells. Human 2B4 became tyrosine phosphorylated following pervanadate-treatment of transfected cells and recruited SHP-2. SAP was also recruited to 2B4 in activated cells. Importantly, the 2B4-SAP interaction prevented the association between 2B4 and SHP-2. These results suggest that the phenotype of XLP may result from perturbed signaling not only through SLAM, but also other cell surface molecules that utilize SAP as a signaling adaptor protein.

Amino Acid Sequence↗
PubMed1999

Electron microscopic evidence against apoptosis as the mechanism of neuronal death in global ischemia.

It has been repeatedly claimed that neuronal death in the hippocampal CA1 sector after untreated global ischemia occurs via apoptosis. This is based largely on DNA laddering, nick end labeling, and light microscopy. Delineation of apoptosis requires fine structural examination to detect morphological events of cell death. We studied the light and ultrastructural characteristics of CA1 injury after 5 min of untreated global ischemia in gerbils. To increase the likelihood of apoptosis, some ischemic gerbils were subjected to delayed postischemic hypothermia, a treatment that mitigates injury and delays the death of some neurons. In these gerbils, 2 d of mild hypothermia was initiated 1, 6, or 12 hr after ischemia, and gerbils were killed 4, 14, or 60 d later. Ischemia without subsequent cooling killed 96% of CA1 neurons by day 4, whereas all hypothermia-treated groups had significantly reduced injury at all survival times (2-67% loss). Electron microscopy of ischemic neurons with or without postischemic hypothermia revealed features of necrotic, not apoptotic, neuronal death even in cells that died 2 months after ischemia. Dilated organelles and intranuclear vacuoles preceded necrosis. Unique to the hypothermia-treated ischemic groups, some salvaged neurons were persistently abnormal and showed accumulation of unusual, morphologically complex secondary lysosomes. These indicate selective mitochondrial injury, because they were closely associated with normal and degenerate mitochondria, and transitional forms between mitochondria and lysosomes occurred. The results show that untreated global ischemic injury has necrotic, not apoptotic, morphology but do not rule out programmed biochemical events of the apoptotic pathway occurring before neuronal necrosis.

Animals↗
PubMed1999

Cloning, characterization, and chromosomal location of a novel human K+-Cl- cotransporter.

Differential display polymerase chain reaction has been used to isolate genes regulated in vascular endothelial cells by the angiogenic factor vascular endothelial cell growth factor (VEGF). Analysis of one of the bands consistently up-regulated by VEGF led us to the identification of a cDNA from a human umbilical vein endothelial cell library that is 77% identical to the human K+-Cl- cotransporter1 (KCC1). We have referred to the predicted protein as K+-Cl- cotransporter 3 (KCC3). Hydrophobicity analysis of the KCC3 amino acid sequence showed an almost identical pattern to KCC1, suggesting 12 membrane-spanning segments, a large extracellular loop with potential N-glycosylation sites, and cytoplasmic N- and C-terminal regions. The KCC3 mRNA was highly expressed in brain, heart, skeletal muscle, and kidney, showing a distinct pattern and size from KCC1 and KCC2. The KCC3 mRNA level in endothelial cells increased on treatment with VEGF and decreased with the proinflammatory cytokine tumor necrosis factor alpha, whereas KCC1 mRNA levels remained unchanged. Stable overexpression of KCC3 cDNA in HEK293 cells produced a glycoprotein of approximately 150 kDa, which was reduced to 120 kDa by glycosidase digestion. An increased initial uptake rate of 86Rb was seen in clones with high KCC3 expression, which was dependent on extracellular Cl- but not Na+ and was inhibitable by the loop diuretic agent furosemide. The KCC3 genomic localization was shown to be 15q13 by fluorescence in situ hybridization. Radiation hybrid analysis placed KCC3 within an area associated with juvenile myoclonic epilepsy. These results suggest KCC3 is a new member of the KCC family that is under distinct regulation from KCC1.

Amino Acid Sequence↗