Activation of TREK currents by riluzole in three subgroups of cultured mouse nodose ganglion neurons

Two-pore domain potassium channels (K2P) constitute major candidates for the regulation of background potassium currents in mammalian cells. Channels of the TREK subfamily are also well positioned to play an important role in sensory transduction due to their sensitivity to a large number of physiological and physical stimuli (pH, mechanical, temperature). Following our previous report describing the molecular expression of different K2P channels in the vagal sensory system, here we confirm that TREK channels are functionally expressed in neurons from the mouse nodose ganglion (mNG). Neurons were subdivided into three groups (A, Ah and C) based on their response to tetrodotoxin and capsaicin. Application of the TREK subfamily activator riluzole to isolated mNG neurons evoked a concentration-dependent outward current in the majority of cells from all the three subtypes studied. Riluzole increased membrane conductance and hyperpolarized the membrane potential by approximately 10 mV when applied to resting neurons. The resting potential was similar in all three groups, but C cells were clearly less excitable and showed smaller hyperpolarization-activated currents at -100 mV and smaller sustained currents at -30 mV. Our results indicate that the TREK subfamily of K2P channels might play an important role in the maintenance of the resting membrane potential in sensory neurons of the autonomic nervous system, suggesting its participation in the modulation of vagal reflexes

A biophysical analysis of the tetratricopeptide repeat-rich mitochondrial import receptor, Tom70, reveals an elongated monomer that is inherently flexible, unstable, and unfolds via a multistate pathway

C1 - Journal Articles RefereedProteins destined for all submitochondrial compartments are translocated across the outer mitochondrial membrane by the TOM (translocase of the outer membrane) complex, which consists of a number of specialized receptor subunits that bind mitochondrial precursor proteins for delivery into the translocation channel. One receptor, Tom70, binds large, hydrophobic mitochondrial precursors. The current model of Tom70-mediated import involves multiple dimers of the receptor recognizing a single molecule of substrate. Here we show via a battery of biophysical and spectroscopic techniques that the cytosolic domain of Tom70 is an elongated monomer. Thermal and urea-induced denaturation revealed that the receptor, which unfolds via a multistate pathway, is a relatively unstable molecule undergoing major conformational change at physiological temperatures. The data suggest that the malleability of the monomeric Tom70 receptor is an important factor in mitochondrial import

Physical properties and optimization of GaBiAs/(Al)GaAs based near-infrared laser diodes grown by MOVPE with up to 4.4% Bi

This paper reports on progress in the development of GaAsBi/(Al)GaAs based lasers grown using metal-organic vapour phase epitaxy and focuses on the underlying processes governing their efficiency and temperature dependence. Room temperature lasing has been achieved in devices with 2.2% Bi and lasing in devices with 4.4% Bi was observed up to 180 K. We show that the device performance can be improved by optimizing both electrical and optical confinement in the laser structures. Analysis of the temperature dependence of the threshold current together with pure spontaneous emission and high hydrostatic pressure measurements indicate that device performance is currently dominated by non-radiative recombination through defects (>80% of the threshold current at room temperature in 2.2% Bi samples) and that to further improve the device performance and move towards longer wavelengths for optical telecommunications (1.3-1.5 μ m) further effort is required to improve and optimize material quality. © 2014 IOP Publishing Ltd

Physical properties and optimization of GaBiAs/(Al)GaAs based near-infrared laser diodes grown by MOVPE with up to 4.4% Bi

This paper reports on progress in the development of GaAsBi/(Al)GaAs based lasers grown using metal-organic vapour phase epitaxy and focuses on the underlying processes governing their efficiency and temperature dependence. Room temperature lasing has been achieved in devices with 2.2% Bi and lasing in devices with 4.4% Bi was observed up to 180 K. We show that the device performance can be improved by optimizing both electrical and optical confinement in the laser structures. Analysis of the temperature dependence of the threshold current together with pure spontaneous emission and high hydrostatic pressure measurements indicate that device performance is currently dominated by non-radiative recombination through defects (>80% of the threshold current at room temperature in 2.2% Bi samples) and that to further improve the device performance and move towards longer wavelengths for optical telecommunications (1.3-1.5 μ m) further effort is required to improve and optimize material quality. © 2014 IOP Publishing Ltd

Properties of hybrid MOVPE/MBE grown GaAsBi/GaAs based near-infrared emitting quantum well lasers

A combined growth approach involving both molecular-beam epitaxy and metal-organic vapor phase epitaxy has been developed to fabricate GaAsBi/GaAs-based quantum well (QW) laser structures with a Bi composition up to 8%. Lasing operation has been demonstrated at room temperature at 1.06 μm in laser diodes containing 3QWs that in turn contain approximately 6% Bi. A 5QW device demonstrated lasing at 1.09 μm at 80 K. Using temperature- and pressure-dependent measurements of stimulated emission as well as pure spontaneous emission measurements, we show that the threshold current of the devices is limited by non-radiative defect-related recombination and an inhomogeneous carrier distribution. This is suspected to be due to inhomogeneity of the QW width as well as non-uniform Bi composition in the active region

The structural basis of fatty acid elongation by the ELOVL elongases

Very long chain fatty acids (VLCFAs) are essential building blocks for the synthesis of ceramides and sphingolipids. The first step in the fatty acid elongation cycle is catalyzed by the 3-keto acyl-coenzyme A (CoA) synthases (in mammals, ELOVL elongases). Although ELOVLs are implicated in common diseases, including insulin resistance, hepatic steatosis and Parkinson’s, their underlying molecular mechanisms are unknown. Here we report the structure of the human ELOVL7 elongase, which comprises an inverted transmembrane barrel surrounding a 35-Å long tunnel containing a covalently attached product analogue. The structure reveals the substrate-binding sites in the narrow tunnel and an active site deep in the membrane. We demonstrate that chain elongation proceeds via an acyl-enzyme intermediate involving the second histidine in the canonical HxxHH motif. The unusual substrate-binding arrangement and chemistry suggest mechanisms for selective ELOVL inhibition, relevant for diseases where VLCFAs accumulate, such as X-linked adrenoleukodystrophy