Role of voltage-gated Kv channels in microglial physiology

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National Library of Canada , Ottawa
SeriesCanadian theses = -- Thèses canadiennes
The Physical Object
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Pagination1 microfiche : negative.
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Open LibraryOL19857115M
ISBN 100612845419
OCLC/WorldCa57061774

The above downsides of various in vitro systems are particularly significant when ion channels such as Kv are being studied, as much of the physiological recordings in vitro are from moderately to fully activated microglial cells and do not fully represent the microglial physiology in Cited by:   Microglia physiology and ion channels.

Description Role of voltage-gated Kv channels in microglial physiology FB2

Studies have highlighted the importance of microglia in brain ionic homeostasis (Annunziato et al., ; Szalay et al., ; Shibata and Suzuki, ).For example, depletion of microglia results in the loss of potassium chloride induced neuronal depolarisation (Szalay et al., ) and the microglia KCa channel has been proposed as a valid Cited by: 7.

Kv, a voltage-gated potassium channel of therapeutic relevance in autoimmunity, is upregulated by activated microglia and mediates amyloid-mediated microglial priming and reactive oxygen species production in vitro.

We hypothesized that Kv channel expression is increased in human AD brain by:   Kv c hannel expression of microglial cells in brain slices from. channels may play a role in microglia physiology A number of voltage-gated ion channels have been identified in.

Voltage-Gated Potassium Channels. Kv channels form an exceedingly diverse group, (iPSCs) may allow a more effective study of microglial ion channel role in neuro-inflammation observed in neurodegenerative diseases such as AD.

Chloride Channels. For this to be realized a clearer picture of human microglial physiology needs to be by: 7. Growing evidences indicated that the voltage-gated potassium channels (Kv) were participated in neuronal damage and microglia function. With the whole cell patch clamp, we found that Meth significantly increased the outward K + currents, therefore, we explored whether Kv, one of the major K + channels expressed in microglia, was involved in.

In mammals, the main feature of juxtaparanodes is the high density of delayed rectifier voltage-gated potassium channels (Kv, Kv and Kvb2 subunits), which might play a role. that a microglial role in the diseased CNS was recognized (, ). these voltage-gated currents became smaller in am- release channels.

Microglial cultures obtained from. Voltage-gated potassium channels (Kv) are the largest group of ion channels. Kv are involved in controlling the resting potential and action potential duration in the heart and brain. Additionally, these proteins participate in cell cycle progression as well as in several other important features in mammalian cell physiology, such as activation, differentiation, apoptosis, and cell volume control.

Other K + Channels with Roles in Microglial Cytokines, Nitric Oxide, and ROS Production. Some studies have also suggested a functional role for Kv and Kv shaker-like voltage-gated K + channels in microglia.

These channels are present in early postnatal microglia but disappear in ramified microglia present in adult rat brain. Kv channels play an important role in regulating restingE m in many types of cells (14, 31, 50, 52).

Inhibition of Kv channels by 4-AP causes membrane depolarization, whereas activation of Kv channels (by nitric oxide) causes membrane hyperpolarization (1, 12, 51). Kv channel involved in Meth mediated microglial damage.

The cells were pre-incubated with 4-AP (1 mM), TEA (5 mM) and MgTx (10 nM) for 30 min before addition of Meth ( mM). Kv, a voltage-gated potassium channel of therapeutic relevance in autoimmunity, is upregulated by activated microglia and mediates amyloid-mediated microglial priming and reactive oxygen.

Request PDF | Microglial Kv Channels as a Potential Target for Alzheimer's Disease | Microglia, the major inflammatory cells of the brain, play a pivotal role in the initiation and progression.

Kv/ K Ca Although K Ca is not a voltage-gated K + channel, its physiological role in lymphocyte proliferation is conceptually very difficult to separate from that of Kv, and we will refer to them together.

As already mentioned, this was the first case where a clear link between K + channels and mitogenesis was established (), and a number of excellent and exhaustive literature. Thus, there is evidence for the impact of Kv channel expression on functional parameters of microglial function, namely on respiratory burst (Khanna et al., ) and proliferation (Kotecha and Schlichter,Chittajallu et al., ).

In the present study we focused on the role of Kv and Kv by interfering with its expression using. There is limited evidence of a role for K + channels in the microglial respiratory burst, with one report showing inhibition by a broad-spectrum K + channel blocker, tetraethylammonium (TEA), and our preliminary work using more selective blockers, which implicated Kv and one or more Ca 2+-activated K + channels (K Ca) (27, 43).

Details Role of voltage-gated Kv channels in microglial physiology FB2

Several possibilities might be considered. Voltage-gated channels respond to changes in the membrane potential (i.e., an influx of Na + or Ca 2+).

Oscillating membrane potentials and Ca 2+ levels have been found in migrating cells (e.g., Petty, ). Thus, K + channels might serve the crucial role of resetting the local signaling apparatus.

Kir channels are characterized by a greater tendency to allow K + to flow into cells (Biggin et al., ). Similar to the structure of the Kv channel, the Kir channel also has a tetrameric structure, and each subunit has two transmembrane domains and one P region.

However, it does not contain a voltage sensor structure in the S4 transmembrane. Cells, an international, peer-reviewed Open Access journal.

The voltage-gated potassium channel, Kv, at the crossroads of glial functions in glioma Despite the current three-modality therapy, which includes surgery, radiation and chemotherapy, the clinical outcome of GBM patients remains poor, with a.

The Na + channel was the first voltage-dependent ion channel to be cloned; it was first isolated and purified from eel electroplax (1).A few years later, voltage-gated K + and Ca 2+ channels were purified and cloned (2,3).Voltage-gated ion channels are the most abundant channels in the heart and share several common structural themes: modular architecture; a central pore with highly conserved.

RESULTS Voltage-gated K + currents. The identity of all β-cells used for electrophysiological analysis in this study was confirmed by immunocytochemistry. Human β-cells thus identified had a membrane capacitance (C slow) of ± pF (n = ) (online appendix Fig.

1).Voltage-gated K + currents were elicited by ms voltage-clamp depolarizations from a holding potential of −70 mV. The diverse roles of various members of a large class of potassium channels, voltage‐gated (Kv) channels, have been largely studied by electrophysiologists in heterologous cells in vitro (ie, outside of a relevant physiological context 2).

Continuous progress in the application of novel research techniques enabled analyses of the effects of. J Physiol () pp – The Journal of Physiology Neuroscience Glucose sensitivity of mouse olfactory bulb neurons is conveyed by a voltage-gated potassium channel Kristal Tucker 2, Sukhee Cho, Nicolas Thiebaud1,2, Michael X.

Henderson 1and Debra Ann Fadool,2 3 1Department of Biological Science, 2Programs in Neuroscience and 3Molecular Biophysics, The.

Voltage-gated potassium (K v) channels are potential targets for both types of therapies. As symptomatic therapies, only two relatively nonspecific blockers of K v channels, 4-aminopyridine (4-AP) and 3,4 diaminopyridine (3,4-DAP), have been tested clinically for their efficacy in the treatment of patients with MS [].

The activity of the voltage-sensitive K+ (Kv) channels varies as a function of the intracellular redox state and metabolism, and several Kv channels act as oxygen sensors.

However, the mechanisms u.

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Voltage-gated K+ (Kv) channel opening repolarizes excitable cells by allowing K+ efflux. Over the last two decades, multiple Kv functions in the nervous system have been found to be unrelated to or beyond the immediate control of excitability, such as shaping action potential contours or regulation of inter-spike frequency.

These functions include neuronal exocytosis and neurite formation. The induction of the expression of both Kv and Kv channels is required for full microglial activation, albeit each channel plays a different role. Upregulation of Kv channels is required for increased nitric oxide production, but leads to cell cycle arrest, while Kv channels do appear to have a role in microglial proliferation and.

Moreover, microglia express H + channels, Na + channels, voltage-gated Ca 2+ channels, Ca 2+-release activated Ca 2+ channels, and voltage-dependent and voltage-independent Cl − channels. With respect to their kinetic and pharmacological properties, most microglial ion channels closely resemble ion channels characterized in other macrophage.

S.Y. Chiu, The Roles of Potassium and Calcium Channels in Physiology and Pathophysiology of Axons, Multiple Sclerosis As A Neuronal Disease, /B/. voltage-gated potassium (Kv) channels regulate cell membrane potential (V m) by controlling the rate of K + exit from the cell and can therefore modulate a large number of cellular processes.

Kv is a Shaker-related Kv channel that is expressed in several tissues. Voltage-Gated Ion Channel. VGICs exist primarily at the resting transmembrane voltage of negative –mV (electrophysiological convention) and experience the absence of a transmembrane voltage, i.e., 0mV, only transiently on a few microseconds timescale during the course of an action potential of a few milliseconds duration (Hodgkin & Huxley, ).