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1.
J Gen Physiol ; 150(5): 731-750, 2018 05 07.
Article in English | MEDLINE | ID: mdl-29626041

ABSTRACT

Dehydroabietic acid (DHAA) is a naturally occurring component of pine resin that was recently shown to open voltage-gated potassium (KV) channels. The hydrophobic part of DHAA anchors the compound near the channel's positively charged voltage sensor in a pocket between the channel and the lipid membrane. The negatively charged carboxyl group exerts an electrostatic effect on the channel's voltage sensor, leading to the channel opening. In this study, we show that the channel-opening effect increases as the length of the carboxyl-group stalk is extended until a critical length of three atoms is reached. Longer stalks render the compounds noneffective. This critical distance is consistent with a simple electrostatic model in which the charge location depends on the stalk length. By combining an effective anchor with the optimal stalk length, we create a compound that opens the human KV7.2/7.3 (M type) potassium channel at a concentration of 1 µM. These results suggest that a stalk between the anchor and the effector group is a powerful way of increasing the potency of a channel-opening drug.


Subject(s)
Abietanes/pharmacology , Ion Channel Gating/drug effects , KCNQ Potassium Channels/chemistry , Shaker Superfamily of Potassium Channels/chemistry , Amino Acid Motifs , Animals , Binding Sites , Humans , KCNQ Potassium Channels/metabolism , Protein Binding , Shaker Superfamily of Potassium Channels/metabolism , Static Electricity , Xenopus
2.
Nano Lett ; 18(5): 3132-3137, 2018 05 09.
Article in English | MEDLINE | ID: mdl-29624405

ABSTRACT

Tunable nanostructures that feature a high surface area are firmly attached to a conducting substrate and can be fabricated efficiently over significant areas, which are of interest for a wide variety of applications in, for instance, energy storage and catalysis. We present a novel approach to fabricate Fe nanoparticles using a pulsed-plasma process and their subsequent guidance and self-organization into well-defined nanostructures on a substrate of choice by the use of an external magnetic field. A systematic analysis and study of the growth procedure demonstrate that nondesired nanoparticle agglomeration in the plasma phase is hindered by electrostatic repulsion, that a polydisperse nanoparticle distribution is a consequence of the magnetic collection, and that the formation of highly networked nanotruss structures is a direct result of the polydisperse nanoparticle distribution. The nanoparticles in the nanotruss are strongly connected, and their outer surfaces are covered with a 2 nm layer of iron oxide. A 10 µm thick nanotruss structure was grown on a lightweight, flexible and conducting carbon-paper substrate, which enabled the efficient production of H2 gas from water splitting at a low overpotential of 210 mV and at a current density of 10 mA/cm2.


Subject(s)
Ferric Compounds/chemistry , Hydrogen/chemistry , Iron/chemistry , Nanostructures/chemistry , Nanotechnology/methods , Water/chemistry , Catalysis , Equipment Design , Magnetic Fields , Magnetics/instrumentation , Magnetics/methods , Magnetite Nanoparticles/chemistry , Magnetite Nanoparticles/ultrastructure , Nanostructures/ultrastructure , Nanotechnology/instrumentation , Plasma Gases/chemistry
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