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B Dethlefs

Publications and source records attributed to B Dethlefs.

9 recordsLinked to original sources
PubMed1995

Topology of the pore-region of a K+ channel revealed by the NMR-derived structures of scorpion toxins.

The architecture of the pore-region of a voltage-gated K+ channel, Kv1.3, was probed using four high affinity scorpion toxins as molecular calipers. We established the structural relatedness of these toxins by solving the structures of kaliotoxin and margatoxin and comparing them with the published structure of charybdotoxin; a homology model of noxiustoxin was then developed. Complementary mutagenesis of Kv1.3 and these toxins, combined with electrostatic compliance and thermodynamic mutant cycle analyses, allowed us to identify multiple toxin-channel interactions. Our analyses reveal the existence of a shallow vestibule at the external entrance to the pore. This vestibule is approximately 28-32 A wide at its outer margin, approximately 28-34 A wide at its base, and approximately 4-8 A deep. The pore is 9-14 A wide at its external entrance and tapers to a width of 4-5 A at a depth of approximately 5-7 A from the vestibule. This structural information should directly aid in developing topological models of the pores of related ion channels and facilitate therapeutic drug design.

Amino Acid Sequence↗
PubMed1992

The Shaw-related potassium channel gene, Kv3.1, on human chromosome 11, encodes the type l K+ channel in T cells.

T lymphocytes exhibit three distinct types of voltage-gated K+ channels, n, n', and l, that are distributed in the T cell lineage according to subset, as well as the cells' activation and developmental status. Type l K+ channels are found sparingly in cytotoxic T cells from normal mice and abundantly in a specific T cell subset (CD4- CD8- Thy1+) from mice with autoimmune disease. Here, we show that the mouse Kv3.1 gene, when expressed in Xenopus oocytes, encodes a channel with properties remarkably similar to those of the l-type channel. Kv3.1 transcripts were found in T cells isolated from the lymph nodes of MRL-lpr mice with systemic lupus erythematosus and in a human lymphoma cell line that also expresses the l channel phenotype. By these criteria, we conclude that Kv3.1 encodes the voltage-gated type l K+ channel in lymphocytes. The Kv3.1 gene maps to human chromosome 11; the related Kv1.1 and Kv3.2 genes are localized on human chromosome 12, while the IsK gene maps to human chromosome 21.

Amino Acid Sequence↗
PubMed1992

Genomic organization, nucleotide sequence, and cellular distribution of a Shaw-related potassium channel gene, Kv3.3, and mapping of Kv3.3 and Kv3.4 to human chromosomes 19 and 1.

Genomic and cDNA clones encoding a novel Shaw-related potassium channel gene have been isolated from mice and humans. The mouse-Kv3.3 gene encodes a protein of 679 amino acids. Unlike the vertebrate Shaker-related genes that have intronless coding regions, mouse Kv3.3 is encoded by at least two exons separated by 3 kb of intervening sequence. The amino-terminal 212 amino acids are encoded by a single exon, and the hydrophobic core of the protein beginning at the S1 transmembrane segment is contained in a separate exon. Multiple Kv3.3-hybridizing transcripts are visible in the mouse brain, liver, thymus, and heart. Using probes derived from a human genomic clone containing the 3' exon of human Kv3.3 (KCNC3), we have localized the gene to human chromosome 19. The related gene, human Kv3.4 (KCNC4), was localized to human chromosome 1.

Amino Acid Sequence↗
PubMed1990

Expression and chromosomal localization of a lymphocyte K+ channel gene.

We recently isolated a family of three closely related mouse K+ channel genes (MK1, MK2, and MK3) with coding regions contained in single uninterrupted exons. Here we have used patch-clamp recordings from Xenopus oocytes injected with mRNA to show that MK3 encodes a channel with biophysical and pharmacological properties indistinguishable from those of voltage-gated type n K+ channels in T cells. In addition, we used the polymerase chain reaction to demonstrate the presence of MK3 mRNA in T cells. These data suggest that MK3 may encode the T-cell voltage-gated type n K+ channel. We also show that MK3 and MK2 are localized on human chromosomes 13 and 12, respectively.

Animals↗
PubMed1987

A rabbit model of staphylococcal blepharitis.

Rabbits immunized with cell wall antigens of Staphylococcus aureus developed blepharitis after topical challenge with viable S aureus. The lids of these rabbits were thickened and erythematous. Crusting was found around the lashes, and the lids developed loss of lashes and hair. Histopathologic examination of lids from rabbits with blepharitis showed a dense leukocytic infiltrate and dilated blood vessels beneath an intact epidermis and palpebral conjunctival epithelium. The infiltrate contained neutrophils as well as mononuclear cells, including macrophages, plasma cells, and lymphocytes. The meibomian glands appeared normal. Gram's staining of lid sections did not show gram-positive cocci. The results of this study suggest that hypersensitivity to the S aureus cell wall, and particularly the ribitol teichoic acid that it contains, plays a role in the pathogenesis of staphylococcal blepharitis.

Animals↗
PubMed1984

Occurrence of phlyctenules after immunization with ribitol teichoic acid of Staphylococcus aureus.

We immunized rabbits to ribitol teichoic acid (RTA), a component of the cell wall of Staphylococcus aureus, by intravenous injections of RTA-sensitized sheep RBCs. Hemagglutination titers to RTA and corneal phlyctenules developed in these rabbits after topical challenge with viable S aureus, but did not develop in control rabbits immunized with unsensitized sheep RBCs. These results suggest that hypersensitivity to RTA, the major antigenic determinant of S aureus, plays a role in the development of corneal phlyctenules.

Animals↗