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Nanotube-Based Membrane Systems
Published in Tuan Vo-Dinh, Nanotechnology in Biology and Medicine, 2017
Lane A. Baker, Charles R. Martin
These ligand-gated ion channel mimics can also be used to detect drug molecules. In these experiments the effects of the hydrophobicity of three drug molecules, bupivacaine, amiodarone, and amitriptyline on the observed transmembrane resistances were investigated. The hydrophobicity of these molecules, a function of molecular weight and polarity, increases in the following order: bupivacaine < amitriptyline < amiodarone. If the hydrophobic nature of these molecules is responsible for the partitioning of these molecules into the membrane, and thus turning on the current, then transition from the off to on state of the membrane would occur at the lowest concentration of amiodarone. This is experimentally observed (Figure 6.21). Bupivacaine is the least hydrophobic of these compounds, and it is also observed experimentally that bupivacaine requires the highest concentration to effect gating from off to on.
Subneuronal Processing of Information by Solitary Waves and Stochastic Processes
Published in Sergey Edward Lyshevski, Nano and Molecular Electronics Handbook, 2018
Danko D. Georgiev, James F. Glazebrook
The underlying theme of this section concerns to an extent how neuron signals are realized as intermittent pulsations through spikes (vis-a-vis action potentials) as propelled along a nerve axon, thus inducing potentials within a configuration of postsynaptic neurons. The postsynaptic potentials (PSPs) undergo spatial and temporal summation in the dendritic tree of each neuron and when the transmembrane voltage at the axonal hillock reaches a threshold value, it triggers an axonal action potential that is transmitted to the presynaptic boutons for subsequent neuromediator release. A physiological principle is that information processing is based mainly on the dynamics of such spiking networks in relationship to the acclaimed model of Hodgkin–Huxley. An action potential on reaching the endpoints of an axon triggers the secretions of neurotransmitters into the synaptic cleft. The neurotransmitters traverse the synaptic cleft and arrive at the membrane of the postsynaptic neuron, activating ligand gated ion channel receptors that allow for electrogenic transmembrane ion fluxes that alter the transmembrane potential and generate postsynaptic electric currents. Such inputs are said to be depolarizing or excitatory if the spiking rate is increased, and in contrast, they are said to be hyperpolarizing or inhibitory if the spiking rate is decreased (otherwise said, greater and diminished probabilities for spiking, respectively). Within a spike train may be found differing behavior: regular, or fast spiking, or bursting. The spike count in an essential way influences the rate coding and in some cases can be realized in terms of a stimulus reconstruction (for further discussions, see e.g., [49]).
An ecotoxicological assessment of the acute toxicity of anatoxin congeners on New Zealand Deleatidium species (mayflies)
Published in Inland Waters, 2020
Laura T. Kelly, Jonathan Puddick, Ken G. Ryan, Olivier Champeau, Susanna A. Wood
Anatoxins bind irreversibly to the nicotinic acetylcholine receptor (nAChR), resulting in cell membrane depolarisation, a process that in vertebrates typically leads to respiratory arrest and death. Invertebrates also possess nAChRs in their central nervous system, and anatoxins may bind to these (Macallan et al. 1988). The invertebrate nAChR is a pentomeric cross-membrane protein, which acts as a ligand gated ion channel and typically consists of 2 α-subunits and a combination of β, γ, δ, and ε subunits in different arrangements (Corringer et al. 2000). As a result, many configurations of the nAChR are possible. Additionally, multiple variations of each of the subunits exist, resulting in different receptor subtypes. The arrangement of subunits and the composition of the nAChR subtypes influences the binding region of the nAChR, resulting in differential receptor binding affinities for sites on each nAChR type (Corringer et al. 2000). In mammals, different nAChR subtypes are found in various systems; for example, muscle-type nAChRs comprise 2 α-subunits—β, δ, and either γ or ε—whereas neuronal-type nAChRs comprise only α and β subunits (Arias 1997). The lack of toxicity of anatoxins to Deleatidium spp. in this study may indicate the presence of different nAChRs, to which anatoxins exhibit differential receptor binding affinities. The function, structure, and diversity of invertebrate nAChRs are poorly understood, despite increased interest due to the use of neonicotinoid pesticides, which interact with nAChRs (Tomizawa and Casida 2001). Ideally, receptors from the target organisms would be isolated and the kinetics of binding examined to provide more information on the binding affinity of anatoxin. Such characterisation, if combined with receptor-binding assays, would provide valuable information on the expected sensitivity of different organisms to anatoxins, enabling more accurate risk assessment and selection of appropriate organisms for toxicology.