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J W Warmke

Publications and source records attributed to J W Warmke.

8 recordsLinked to original sources
PubMed1997

The Drosophila erg K+ channel polypeptide is encoded by the seizure locus.

The eag family of K+ channels contains three known subtypes: eag, elk, and erg. Genes representing the first two subtypes have been identified in flies and mammals, whereas the third subtype has been defined only by the human HERG gene, which encodes an inwardly rectifying channel that is mutated in some cardiac arrhythmias. To establish the predicted existence of a Drosophila gene in the erg subfamily and to learn more about the structure and biological function of channels within this subfamily, we undertook a search for the Drosophila counterpart of HERG. Here we report the isolation and characterization of the Drosophila erg gene. We show that it corresponds with the previously identified seizure (sei) locus, mutations of which cause a temperature-sensitive paralytic phenotype associated with hyperactivity in the flight motor pathway. These results yield new insights into the structure and evolution of the eag family of channels, provide a molecular explanation for the sei mutant phenotype, and demonstrate the important physiological roles of erg-type channels from invertebrates to mammals.

Amino Acid Sequence↗
PubMed1997

Functional expression of Drosophila para sodium channels. Modulation by the membrane protein TipE and toxin pharmacology.

The Drosophila para sodium channel alpha subunit was expressed in Xenopus oocytes alone and in combination with tipE, a putative Drosophila sodium channel accessory subunit. Coexpression of tipE with para results in elevated levels of sodium currents and accelerated current decay. Para/TipE sodium channels have biophysical and pharmacological properties similar to those of native channels. However, the pharmacology of these channels differs from that of vertebrate sodium channels: (a) toxin II from Anemonia sulcata, which slows inactivation, binds to Para and some mammalian sodium channels with similar affinity (Kd congruent with 10 nM), but this toxin causes a 100-fold greater decrease in the rate of inactivation of Para/TipE than of mammalian channels; (b) Para sodium channels are >10-fold more sensitive to block by tetrodotoxin; and (c) modification by the pyrethroid insecticide permethrin is >100-fold more potent for Para than for rat brain type IIA sodium channels. Our results suggest that the selective toxicity of pyrethroid insecticides is due at least in part to the greater affinity of pyrethroids for insect sodium channels than for mammalian sodium channels.

Animals↗
PubMed1995

Characterization of tissue-expressed alpha subunits of the high conductance Ca(2+)-activated K+ channel.

Purified high conductance calcium-activated potassium (maxi-K) channels from tracheal smooth muscle have been shown to consist of a 60-70-kDa alpha subunit, encoded by the slo gene, and a 31-kDa beta subunit. Although the size of the beta subunit is that expected for the product of the gene encoding this protein, the size of the alpha subunit is smaller than that predicted from the slo coding region. To determine the basis for this discrepancy, sequence-directed antibodies have been raised against slo. These antibodies specifically precipitate the in vitro translation product of mslo, which yields an alpha subunit of the expected molecular mass (135 kDa). Immunostaining experiments employing smooth muscle sarcolemma, skeletal muscle T-tubules, as well as membranes derived from GH3 cells reveal the presence of an alpha subunit with an apparent molecular mass of 125 kDa. The difference in size of the alpha subunit as expressed in these membranes and the purified preparations is due to a highly reproducible proteolytic decay that occurs mostly at an advanced stage of the maxi-K channel purification. In the purified maxi-K channel preparations investigated, the full-length alpha subunit, an intermediate size product of 90 kDa, and the 65-kDa polypeptide, as well as other smaller fragments can be detected using appropriate antibodies. Proteolysis occurs exclusively at two distinct positions within the long C-terminal tail of slo. In addition, evidence for the tissue expression of distinct splice variants in membrane-bound as well as purified maxi-K channels is presented.

Amino Acid Sequence↗
PubMed1995

HERG, a human inward rectifier in the voltage-gated potassium channel family.

In contrast to other members of the Eag family of voltage-gated, outwardly rectifying potassium channels, the human eag-related gene (HERG) has now been shown to encode an inwardly rectifying potassium channel. The properties of HERG channels are consistent with the gating properties of Eag-related and other outwardly rectifying, S4-containing potassium channels, but with the addition of an inactivation mechanism that attenuates potassium efflux during depolarization. Because mutations in HERG cause a form of long-QT syndrome, these properties of HERG channel function may be critical to the maintenance of normal cardiac rhythmicity.

Animals↗
PubMed1994

A family of potassium channel genes related to eag in Drosophila and mammals.

We have identified a conserved family of genes related to Drosophila eag, which encodes a distinct type of voltage-activated K+ channel. Three related genes were recovered in screens of cDNA libraries from Drosophila, mouse, and human tissues. One gene is the mouse counterpart of eag; the other two represent additional subfamilies. The human gene maps to chromosome 7. Family members share at least 47% amino acid identity in their hydrophobic cores and all contain a segment homologous to a cyclic nucleotide-binding domain. Sequence comparisons indicate that members of this family are most closely related to vertebrate cyclic nucleotide-gated cation channels and plant inward-rectifying K+ channels. The existence of another family of K+ channel structural genes further extends the known diversity of K+ channels and has important implications for the structure, function, and evolution of the superfamily of voltage-sensitive ion channels.

Amino Acid Sequence↗
PubMed1989

Co-localization to chromosome bands 99E1-3 of the Drosophila melanogaster myosin light chain-2 gene and a haplo-insufficient locus that affects flight behavior.

Using overlapping synthetic deficiencies, we find that a haplo-insufficient locus affecting flight behavior and the myosin light chain-2 gene co-map to the Drosophila melanogaster polytene chromosome interval 99D9-E1 to 99E2-3. From screening over 9000 EMS-treated chromosomes, we obtained alleles of two complementation groups that map to this same interval. One of these complementation groups lfm(3)99Eb, exhibits dominant flightless behavior; thus, flightless behavior of the deficiency is in all likelihood due to hemizygosity of this single locus. Rescue of flightless behavior by a duplication indicates that the single allele, E38, of the Ifm(3)99Eb complementation group is a hypomorph. Based upon its map position and a reduction in concentration of myosin light chain-2 mRNA in heterozygotes, we propose that Ifm(3)Eb(E38) is a mutant allele of the myosin light chain-2 gene. Our genetic analysis also resulted in the identification of four dominant flightless alleles of an unlinked locus, l(3)nc99Eb, that exhibits dominant lethal synergism with Ifm(3)99Eb.

Alleles↗