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Alison M. Gurney

Bio: Alison M. Gurney is an academic researcher from University of Manchester. The author has contributed to research in topics: Membrane potential & Depolarization. The author has an hindex of 32, co-authored 90 publications receiving 3817 citations. Previous affiliations of Alison M. Gurney include St Thomas' Hospital & University of Nevada, Reno.


Papers
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Journal ArticleDOI
TL;DR: Evolution utilised this gradient together with an ability of Ca(2+) to interact with many biological molecules to create the most widespread and versatile signalling system, controlling the majority of cellular processes and executing complex routines of intercellular communications.

255 citations

Journal ArticleDOI
TL;DR: Interstitial cells of Cajal are located on the boundary of smooth muscle bundles in the guinea pig bladder, suggesting that they could act as pacemakers or intermediaries in the transmission of nerve signals to smooth muscle cells.

253 citations

Journal ArticleDOI
TL;DR: The results are consistent with the idea that intracellular ATP can directly modulate the resting potential by inhibition of K+ channels, and it is proposed that this ATP-sensitive K+ current plays an important role in the maintenance of the rested potential in arterial muscle.
Abstract: ATP-sensitive K+ (KATP) channels have been proposed to be the target for hyperpolarizing vasodilators. However, the existence of a whole cell KATP current that can regulate membrane potential has not been demonstrated in vascular muscle. Using the patch-clamp technique, we have examined the effects of varying intracellular ATP on membrane potential and currents in isolated rabbit pulmonary arterial smooth muscle cells. With 1 mM ATP in the pipette, cells had a mean resting potential of -55 mV. When ATP was omitted, the resting potential became significantly more hyperpolarized (-70 mV) and the depolarizing response to the KATP-channel blocker, glibenclamide, was potentiated. In contrast, the hyperpolarizing effect of lemakalim was reduced. These hyperpolarized resting potentials were associated with increased activity of a basal, glibenclamide-sensitive time-independent K+ current. Furthermore, flash photolysis of ATP, 3-O-[1(4,5-dimethoxy-2-nitrophenyl)ethyl] ester, disodium salt ("caged ATP") in ATP-depleted cells caused rapid depolarization (less than 1 s) and block of the background K+ current. Our results are consistent with the idea that intracellular ATP can directly modulate the resting potential by inhibition of K+ channels. We propose that this ATP-sensitive K+ current plays an important role in the maintenance of the resting potential in arterial muscle.

185 citations

Journal ArticleDOI
TL;DR: Strong evidence is provided that the two-pore domain K+ channel, TASK-1, mediates a noninactivating, background K+ current (IKN), which sets the resting membrane potential in rabbit pulmonary artery smooth muscle cells (PASMCs).
Abstract: Pulmonary vascular tone is strongly influenced by the resting membrane potential of smooth muscle cells, depolarization promoting Ca2+ influx, and contraction. The resting potential is determined l...

178 citations

Journal ArticleDOI
TL;DR: CPA activated a sustained inward current at negative membrane potentials, which persisted in cells dialyzed with BAPTA, showed a near linear dependence on membrane potential when Cs+ was the main intracellular cation, and was blocked by Ni2+, Cd2+, and SKF96365 at concentrations preventing contraction.
Abstract: Cation channels activated by Ca2+ store depletion have been proposed to mediate Ca2+ influx in vascular smooth muscle cells. The aim of this study was to determine if store-operated channels have a...

174 citations


Cited by
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Journal ArticleDOI
TL;DR: Current studies indicate that even in the normal brain, microglia have highly motile processes by which they scan their territorial domains, and microglial cells are considered the most susceptible sensors of brain pathology.
Abstract: Microglial cells are the resident macrophages in the central nervous system. These cells of mesodermal/mesenchymal origin migrate into all regions of the central nervous system, disseminate through the brain parenchyma, and acquire a specific ramified morphological phenotype termed "resting microglia." Recent studies indicate that even in the normal brain, microglia have highly motile processes by which they scan their territorial domains. By a large number of signaling pathways they can communicate with macroglial cells and neurons and with cells of the immune system. Likewise, microglial cells express receptors classically described for brain-specific communication such as neurotransmitter receptors and those first discovered as immune cell-specific such as for cytokines. Microglial cells are considered the most susceptible sensors of brain pathology. Upon any detection of signs for brain lesions or nervous system dysfunction, microglial cells undergo a complex, multistage activation process that converts them into the "activated microglial cell." This cell form has the capacity to release a large number of substances that can act detrimental or beneficial for the surrounding cells. Activated microglial cells can migrate to the site of injury, proliferate, and phagocytose cells and cellular compartments.

2,998 citations

Journal ArticleDOI
TL;DR: The main conclusions of this review are: 1) regulation of arterial smooth muscle membrane potential through activation or inhibition of K+ channel activity provides an important mechanism to dilate or constrict arteries; 2) KV, KCa, KIR, and KATP channels serve unique functions in the regulation of artery membrane potential
Abstract: This review examines the properties and roles of the four types of K+ channels that have been identified in the cell membrane of arterial smooth muscle cells. 1) Voltage-dependent K+ (KV) channels increase their activity with membrane depolarization and are important regulators of smooth muscle membrane potential in response to depolarizing stimuli. 2) Ca(2+)-activated K+ (KCa) channels respond to changes in intracellular Ca2+ to regulate membrane potential and play an important role in the control of myogenic tone in small arteries. 3) Inward rectifier K+ (KIR) channels regulate membrane potential in smooth muscle cells from several types of resistance arteries and may be responsible for external K(+)-induced dilations. 4) ATP-sensitive K+ (KATP) channels respond to changes in cellular metabolism and are targets of a variety of vasodilating stimuli. The main conclusions of this review are: 1) regulation of arterial smooth muscle membrane potential through activation or inhibition of K+ channel activity provides an important mechanism to dilate or constrict arteries; 2) KV, KCa, KIR, and KATP channels serve unique functions in the regulation of arterial smooth muscle membrane potential; and 3) K+ channels integrate a variety of vasoactive signals to dilate or constrict arteries through regulation of the membrane potential in arterial smooth muscle.

2,113 citations

Journal ArticleDOI
TL;DR: A new group of fluorescent indicators with visible excitation and emission wavelengths has been synthesized for measurements of cytosolic free Ca2+.

1,631 citations

Patent
06 Jun 1995
TL;DR: In this article, a synthetic strategy for the creation of large scale chemical diversity is presented, where solid phase chemistry, photolabile protecting groups, and photolithography are used to achieve light-directed spatially addressable parallel chemical synthesis.
Abstract: A synthetic strategy for the creation of large scale chemical diversity. Solid-phase chemistry, photolabile protecting groups, and photolithography are used to achieve light-directed spatially-addressable parallel chemical synthesis. Binary masking techniques are utilized in one embodiment. A reactor system, photoremovable protective groups, and improved data collection and handling techniques are also disclosed. A technique for screening linker molecules is also provided.

1,312 citations

Patent
07 Jun 1990
TL;DR: In this paper, a method and apparatus for preparation of a substrate containing a plurality of sequences is described, where a set of photoremovable groups are attached to a surface of the substrate and selected regions of the surface are exposed to light so as to activate the selected areas.
Abstract: A method and apparatus for preparation of a substrate containing a plurality of sequences. Photoremovable groups are attached to a surface of a substrate. Selected regions of the substrate are exposed to light so as to activate the selected areas. A monomer, also containing a photoremovable group, is provided to the substrate to bind at the selected areas. The process is repeated using a variety of monomers such as amino acids until sequences of a desired length are obtained. Detection methods and apparatus are also disclosed.

1,171 citations