Main Menu (Mobile)- Block

Main Menu - Block

janelia7_blocks-janelia7_fake_breadcrumb | block
Koyama Lab / Publications
custom | custom

Filter

facetapi-PV5lg7xuz68EAY8eakJzrcmwtdGEnxR0 | block
facetapi-021SKYQnqXW6ODq5W5dPAFEDBaEJubhN | block
general_search_page-panel_pane_1 | views_panes

3 Publications

Showing 1-3 of 3 results
Your Criteria:
    09/11/03 | In vivo imaging of C. elegans mechanosensory neurons demonstrates a specific role for the MEC-4 channel in the process of gentle touch sensation.
    Suzuki H, Kerr R, Bianchi L, Frøkjaer-Jensen C, Slone D, Xue J, Gerstbrein B, Driscoll M, Schafer WR
    Neuron. 2003 Sep 11;39(6):1005-17

    In the nematode C. elegans, genes encoding components of a putative mechanotransducing channel complex have been identified in screens for light-touch-insensitive mutants. A long-standing question, however, is whether identified MEC proteins act directly in touch transduction or contribute indirectly by maintaining basic mechanoreceptor neuron physiology. In this study, we used the genetically encoded calcium indicator cameleon to record cellular responses of mechanosensory neurons to touch stimuli in intact, behaving nematodes. We defined a gentle touch sensory modality that adapts with a time course of approximately 500 ms and primarily senses motion rather than pressure. The DEG/ENaC channel subunit MEC-4 and channel-associated stomatin MEC-2 are specifically required for neural responses to gentle mechanical stimulation but do not affect the basic physiology of touch neurons or their in vivo responses to harsh mechanical stimulation. These results distinguish a specific role for the MEC channel proteins in the process of gentle touch mechanosensation.

    View Publication Page
    09/05/03 | Visualization of the domain structure of an L-type Ca2+ channel using electron cryo-microscopy.
    Wolf M, Eberhart A, Glossmann H, Striessnig J, Grigorieff N
    Journal of Molecular Biology. 2003 Sep 05;332(1):171-82

    The three-dimensional structure of the skeletal muscle voltage-gated L-type calcium channel (Ca(v)1.1; dihydropyridine receptor, DHPR) was determined using electron cryo-microscopy and single-particle averaging. The structure shows a single channel complex with an approximate total molecular mass of 550 kDa, corresponding to the five known subunits of the DHPR, and bound detergent and lipid. Features visible in our structure together with antibody labeling of the beta and alpha(2) subunits allowed us to assign locations for four of the five subunits within the structure. The most striking feature of the structure is the extra-cellular alpha(2) subunit that protrudes from the membrane domain in close proximity to the alpha(1) subunit. The cytosolic beta subunit is located close to the membrane and adjacent to subunits alpha(1), gamma and delta. Our structure correlates well with the functional and biochemical data available for this channel and suggests a three-dimensional model for the excitation-contraction coupling complex consisting of DHPR tetrads and the calcium release channel.

    View Publication Page
    09/01/03 | Design, synthesis, and development of novel caprolactam anticonvulsants.
    Grimm JB, Stables JP, Brown ML
    Bioorganic & Medicinal Chemistry. 2003 Sep 1;11(18):4133-41

    Epilepsy afflicts 1-2% of the world’s population and often goes untreated; nearly 70% of those with a form of epilepsy fail to receive proper treatment. Therefore, there is great demand for the design of novel, effective anticonvulsants to combat epilepsy in its numerous forms. Previously, alpha-hydroxy-alpha-phenylcaprolactam was found to have rather potent antiepileptic activity [anti-maximal electroshock (MES) ED(50)=63 mg/kg and anti-subcutaneous Metrazol (scMet) ED(50)=74 mg/kg] when administered intraperitoneally in mice. We focused our attention on the development of this compound through traditional medicinal chemistry techniques-including the Topliss approach, isosteric replacement, methylene insertion, and rigid analogue approach-in the hopes of determining the effect of caprolactam alpha-substitution and other structural modifications on anticonvulsant activity. A number of the desired targets were successfully synthesized and submitted to the Anticonvulsant Screening Program of the National Institute of Neurological Disorders and Stroke (NINDS). Phase I results were quite promising for at least three of the compounds: alpha-ethynyl-alpha-hydroxycaprolactam (10), alpha-benzyl-alpha-hydroxycaprolactam (11), and alpha-hydroxy-alpha-(phenylethynyl)caprolactam (13). Phase II results for 11 strongly suggested it as a new structural class for further development, as it exhibited an anti-MES T.I. in excess of 4.0. Further, the potent activity of 13 in all models also pointed to the substituted alkynylcaprolactams as a new anticonvulsant structural class.

    View Publication Page