PubMed Health⌕ Search

Biomedical subjects

T Jegla

Publications and source records attributed to T Jegla.

9 recordsLinked to original sources
PubMed2007

Role of a novel photopigment, melanopsin, in behavioral adaptation to light.

Adaptation to changes in the ambient light is of critical importance to life. In mammals, three principal photoadaptation mechanisms depend on ocular photoreception and exhibit spectral sensitivity suggestive of the opsin class of photopigment(s). These include rapid adaptation of the visual system to the ambient light by pupil constriction, direct modulation of neuroendocrine function and entrainment of the circadian clock to the day:night cycle. Surprisingly, these processes can largely function independent of classical rod/cone photoreceptors, suggesting a novel opsin-based signaling mechanism. They appear to involve a recently discovered network of intrinsically photosensitive retinal ganglion cells that make direct or indirect axonal connections to brain centers regulating photoadaptive behaviors. The discovery of a novel opsin, melanopsin, in these cells has offered an exciting entry point to explore, at the molecular level, how mammals adapt to their light environment. There is now genetic proof of a principal role for melanopsin in all three major photoadaptation processes.

Adaptation, Biological↗
PubMed2001

Characterization of KCNQ5/Q3 potassium channels expressed in mammalian cells.

Heteromeric KCNQ5/Q3 channels were stably expressed in Chinese Hamster ovary cells and characterized using the whole cell voltage-clamp technique. KCNQ5/Q3 channels were activated by the novel anticonvulsant, retigabine (EC(50) 1.4 microM) by a mechanism that involved drug-induced, leftward shifts in the voltage-dependence of channel activation (-31.8 mV by 30 microM retigabine). KCNQ5/Q3 channels were inhibited by linopirdine (IC(50) 7.7 microM) and barium (IC(50) 0.46 mM), at concentrations similar to those required to inhibit native M-currents. These findings identify KCNQ5/Q3 channels as a molecular target for retigabine and raise the possibility that activation of KCNQ5/Q3 channels may be responsible for some of the anti-convulsant activity of this agent. Furthermore, the sensitivity of KCNQ5/Q3 channels to linopirdine supports the possibility that potassium channels comprised of KCNQ5 and KCNQ3 may make a contribution to native M-currents.

Animals↗
PubMed2000

Retigabine, a novel anti-convulsant, enhances activation of KCNQ2/Q3 potassium channels.

Retigabine [N-(2-amino-4-[fluorobenzylamino]-phenyl) carbamic acid; D-23129] is a novel anticonvulsant, unrelated to currently available antiepileptic agents, with activity in a broad range of seizure models. In the present study, we sought to determine whether retigabine could enhance current through M-like currents in PC12 cells and KCNQ2/Q3 K(+) channels expressed in Chinese hamster ovary cells (CHO-KCNQ2/Q3). In differentiated PC12 cells, retigabine enhanced a linopirdine-sensitive current. The effect of retigabine was associated with a slowing of M-like tail current deactivation in these cells. Retigabine (0.1 to 10 microM) induced a potassium current and hyperpolarized CHO cells expressing KCNQ2/Q3 cells but not in wild-type cells. Retigabine-induced currents in CHO-KCNQ2/Q3 cells were inhibited by 60.6 +/- 11% (n = 4) by the KCNQ2/Q3 blocker, linopirdine (10 microM), and 82.7 +/- 5.4% (n = 4) by BaCl(2) (10 mM). The mechanism by which retigabine enhanced KCNQ2/Q3 currents involved large, drug-induced, leftward shifts in the voltage dependence of channel activation (-33.1 +/- 2.6 mV, n = 4, by 10 microM retigabine). Retigabine shifted the voltage dependence of channel activation with an EC(50) value of 1.6 +/- 0.3 microM (slope factor was 1.2 +/- 0.1, n = 4 to 5 cells per concentration). Retigabine (0.1 to 10 microM) also slowed the rate of channel deactivation, predominantly by increasing the contribution of a slowly deactivating tail current component. Our findings identify KCNQ2/Q3 channels as a molecular target for retigabine and suggest that activation of KCNQ2/Q3 channels may be responsible for at least some of the anticonvulsant activity of this agent.

Animals↗
PubMed1997

A novel subunit for shal K+ channels radically alters activation and inactivation.

Shal (Kv4) potassium channel genes encode classical subthreshold A-currents, and their regulation may be a key factor in determining neuronal firing frequency. The inactivation rate of Shal channels is increased by a presently unidentified class of proteins in both Drosophila and mammals. We have cloned a novel Shal channel subunit (jShalgamma1) from the jellyfish Polyorchis penicillatus that alters Shal currents from both invertebrates and vertebrates. When co-expressed with the conserved jellyfish Shal homolog jShal1, jShalgamma1 dramatically changes both the rate of inactivation and voltage range of activation and steady-state inactivation. jShalgamma1 provides fast inactivation by a classic N-type mechanism, which is independent of its effects on voltage dependence. jShalgamma1 forms functional channels only as a heteromultimer, and jShalgamma1 + jShal1 heteromultimers are functional only in a 2:2 subunit stoichiometry.

Amino Acid Sequence↗
PubMed1996

Eight potassium channel families revealed by the C. elegans genome project.

The wealth of accumulating data from the Caenorhabditis elegans genome sequencing project has rapidly accelerated the discovery of novel potassium channel genes and now places within reach the possibility of describing the total complement of potassium channels used by an individual species. Using annotated GenBank sequences, BLAST searches of unfinished sequences and degenerate oligonucleotide polymerase chain reaction (PCR) screens, we have identified and compiled genes for 38 C. elegans potassium channel and two cyclic nucleotide-gated cation channel subunits, representing eight conserved multigene families. Novel families of potassium channel genes were revealed, as well as conserved homologues of all known vertebrate families. Two separate families represent C. elegans homologues for human potassium channels recently implicated in hereditary long QT arrhythmias. Of particular note is an exceptionally large class of at least 23 genes with a novel subunit structure having two tandem 'P' domains; these channels may form as dimers in contrast to all other potassium channel types which form as tetramers. The 40 potassium channel genes are evenly distributed on all six C. elegans chromosomes, with the exception of the instances of gene clustering on the fifth and X chromosomes.

Amino Acid Sequence↗
PubMed1995

A multigene family of novel K+ channels from Paramecium tetraurelia.

Paramecium tetraurelia has an excitable membrane with electrical properties resembling those of nerve and muscle cells from metazoans. However, the relationship between the molecules underlying electrical excitability in Paramecium and those found in metazoans has been unexplored. Using a PCR-based screen, we identified a multigene family of putative potassium channels in the ciliate protist Paramecium tetraurelia. Two distinct genomic clones were isolated, each encoding an apparently complete channel, Pak1 and Pak2. Fragments of three additional genes were also isolated. The deduced amino acid sequences appear to define a family of novel K+ channel genes which are only distantly related to metazoan potassium channels; the K+-selective pore region is exceptionally well conserved, but outside this region, PaK1 and PaK2 bear little resemblance to the metazoan voltage-gated K+ channels, Shaker Shal, Shab or Shaw. The uniqueness of this large set of K+ channel genes may be accounted for by the distinct evolutionary pressures at play in the single celled Paramecium versus the multicellular Metazoans. Since a large number of K+ channel mutants exist in Paramecium, the sequences of the K+ channel gene family reported here may represent a significant step towards the molecular characterization of these important behavioral mutants.

Amino Acid Sequence↗
PubMed1995

Multiple Shaker potassium channels in a primitive metazoan.

Voltage-gated potassium channels are critical elements in providing functional diversity in nervous systems. The diversity of voltage-gated K+ channels in modern triploblastic metazoans (such as mollusks, arthropods and vertebrates) is provided primarily by four gene subfamilies (Shaker, Shal, Shab, and Shaw), but there has been no data from the ancient diploblastic metazoans until now. Diploblasts, represented by jellyfish and other coelenterates, arose during the first major metazoan radiation and are the most structurally primitive animals to have true nervous systems. By comparing the K+ channels of diploblasts and triploblasts, we may determine the fundamental set of K+ channels present in the first nervous systems. We now report the isolation of two Shaker subfamily cDNA clones, jShak1 and jShak2, from the hydrozoan jellyfish Polyorchis penicillatus (Phylum Cnidaria). JShak1 and jShak2 express transient outward currents in Xenopus oocytes most similar to Shaker currents from Drosophila in their rates of inactivation and recovery from inactivation. The finding of multiple Shaker subfamily genes is significant in that multiple Shaker genes also exist in mammals. In Drosophila, multiple Shaker channels are also produced, but by a mechanism of alternative splicing. Thus, the Shaker K+ channel subfamily had an established functional identity prior to the first major radiation of metazoans, and multiple forms of Shaker channels have been independently selected for in a wide range of metazoans.

Amino Acid Sequence↗
PubMed1994

Molecular evolution of K+ channels in primitive eukaryotes.

Cnidarians and ciliate protozoans represent evolutionary interesting phylogenetic groups for the study of K+ channel evolution. Cnidaria is a primitive metazoan phylum consisting of simple diploblast organisms which have few tissue types such as jellyfish, hydra, sea anemones, and corals. Their divergence from the rest of the metazoan line may predate the radiation of the major triploblast phyla by several hundred million years (Morris, 1993). Cnidarians are the most primitive metazoans to have an organized nervous system. Thus, comparing K+ channels cloned from cnidarians to those cloned from more advanced metazoans may reveal which types of K+ channel are most fundamental to electrical excitability in the nervous system. In contrast, channels in ciliate protozoans such as Paramecium may not have been designed to send electrical signals between cells, but simply to control the behavior, such as an avoidance reaction, of a single cell. Hence, comparing cloned Paramecium K+ channels to K+ channels cloned from cnidarians and other metazoans may reveal which types of K+ channel are most fundamental to electrical excitability in eukaryotes, and which K+ channels are specialized for neuronal signaling. Potassium channels are involved in a diversity of tasks and are universally present in eukaryotes. K+ channels set the resting membrane potentials of most metazoan and protozoan cells and are fundamental components of membrane electrical activity in virtually all eukaryotic systems. These channels control the shape, duration and frequency of metazoan action potentials and are known to participate in the action potentials of protozoans, fungi and plants as well (Hille, 1992). Voltage-clamp recordings have shown that a various assortment of voltage-gated K+ channels as well as Ca(2+)-activated K+ channels are widespread in eukaryotes (Hille, 1992). Thus, K+ channels appear to be crucial to behavioral responses in all classes of eukaryotes, including locomotion in metazoans and protozoans, and rapid growth responses and cell shape changes in plants. K+ channel diversity is by far the greatest in metazoans, which have made a strong commitment to electrically excitable cellular networks. There is an apparent need for a great diversity of K+ channel subtypes in these metazoans. Over 50 K+ channel sequences from many distinct gene families have been reported so far, and all but two (both from plants) have been found in triploblast metazoans. The complex needs of neuronal integration and neuromuscular transmission in triploblasts require exquisite control of cellular excitability. This is in large part achieved by an extensive and diverse set of K+ channels.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗