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Query: UMLS:C0016632 (Fox)
 1,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The adenosine analogue 2-chloroadenosine (CADO) reduced the duration of calcium-dependent action potentials (CAPs) in mouse dorsal root ganglion (DRG) neurones in culture, by reducing voltage-activated calcium conductance (Macdonald, Skerritt & Werz, 1986). Using the single-electrode voltage clamp technique, we recorded three calcium current components in these neurones, the transient low-threshold (T), transient high-threshold (N) and slowly inactivating high-threshold (L) currents, as described previously (Nowycky, Fox & Tsien, 1985; Gross & Macdonald, 1987). CADO (100 microM) had no effect on the isolated T and L currents. In contrast, CADO reduced calcium currents evoked at clamp potentials positive to -20 mV from holding potentials (Vh) near the resting membrane potential; under these conditions, the calcium current consisted primarily of N and L calcium current components. 2. This effect of CADO was not voltage dependent. CADO reduced the magnitude of the calcium current without affecting the voltage dependence of the calcium current-voltage relation. In addition, similar reductions of calcium current were observed when currents were evoked from Vh of -60 or -80 mV. 3. In order to determine if a guanine nucleotide-binding (G) protein was involved in the CADO effect on calcium current, cultures were pre-treated with pertussis toxin (PT) for at least four hours. PT (100 ng/ml) reduced or abolished the CADO-induced reduction of CAP duration and calcium current. 4. Since CADO inhibits adenylate cyclase through the PT-sensitive G protein, Gi, we compared the effects of CADO and 8-Br-adenosine 3',5'-cyclic-monophosphate (8-Br-cyclic AMP) on calcium current. The effect of 8-Br-cyclic AMP was voltage dependent, unlike that of CADO. 8-Br-cyclic AMP reduced calcium currents evoked from Vh = -65 mV, but had no effect on currents evoked from Vh = -85 mV. 5. We conclude that the adenosine agonist CADO reduced CAP duration in mouse DRG neurones by selectively reducing the N current component, and that the coupling between the adenosine receptor and the calcium channel required a PT-sensitive G protein. The CADO effect was unlikely, however, to be due to modulation of adenylate cyclase activity.
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PMID:2-Chloroadenosine reduces the N calcium current of cultured mouse sensory neurones in a pertussis toxin-sensitive manner. 261 35

In this review, we have concentrated on the parallels between the cellular properties of the NMDA receptor and a variety of functional properties within sensory and motor systems. Of course, the NMDA channel exists within the cell in conjunction with a variety of other channels, including non-NMDA channels. Although the NMDA receptor is unique in a cellular sense--it is the only ligand-gated channel that is also voltage dependent and calcium permeable--it is not unique in a functional sense. A cell that has non-NMDA receptors and voltage-sensitive channels will also exhibit nonlinear behavior. Moreover, Buhrle & Sonnhof (1983) demonstrated some time ago that calcium flows into frog motor neurons through more than one type of calcium channel. The contribution to the inflow of calcium from NMDA channels may vary from cell to cell and could easily be a minor proportion of the total. Many authors have pointed out that the NMDA channel has a low conductance at a resting potential of -70 mV. However, many cells in the nervous system are depolarized from -70 mV by excitatory input. Thus, as pointed out above. NMDA receptors make a contribution to the tonic or spontaneous activity of cells in both visual cortex and spinal cord. In practice, many cells are probably working in a range of membrane potentials where the NMDA channels are always open to some extent. Even in the hippocampal slice where a substantial amount of afferent input is removed, NMDA receptors contribute to spontaneous activity (Sah et al 1989). Does the NMDA receptor act as a switch? Does it act as an AND gate? The suggestion that it may act as a switch comes from work on LTP in the hippocampus, which is readily produced by high-frequency stimulation and is abolished by APV. However, activation of the NMDA receptor is only the first in a sequence of reactions leading to LTP: In theory, switch-like behavior could also be produced by calcium-buffering systems within dendritic spines, or by enzymatic processes (Lisman 1985; Zador et al 1990). Fox & Daw (1992) have modeled the action of NMDA and non-NMDA receptors that are activated in parallel with each other, and shown that the occurrence of switch-like behavior depends on the relative density of NMDA versus non-NMDA receptors. Switch-like behavior is not seen in the visual cortex, but might be seen in the hippocampus if the relative density of NMDA receptors there was higher than in the visual cortex.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The role of NMDA receptors in information processing. 846 Aug 91

Presynaptic CaV2.2 (N type) calcium channels gate the influx of calcium ions to trigger transmitter release. We have previously demonstrated at the chick ciliary ganglion presynaptic calyx terminal that the bulk of these channels are highly resistant to voltage dependent inactivation [E.F. Stanley, G. Goping, Characterization of a calcium current in a vertebrate cholinergic presynaptic nerve terminal, J. Neurosci. 11 (1991) 985-993; E.F. Stanley, Syntaxin I modulation of presynaptic calcium channel inactivation revealed by botulinum toxin C1, Eur. J. Neurosci. 17 (2003) 1303-1305; E.F. Stanley, R.R. Mirotznik, Cleavage of syntaxin prevents G-protein regulation of presynaptic calcium channels, Nature (Lond.) 385 (1997) 340-343]. Recent studies have suggested that CaV2.2 can be rendered inactivation resistant when expressed with the palmitoylated beta2A subunit and that this effect can be eliminated by tunicamycin, a general inhibitor of dynamic palmitoylation [J.H. Hurley, A.L. Cahill, K.P. Currie, A.P. Fox, The role of dynamic palmitoylation in Ca(2+) channel inactivation, Proc. Natl. Acad. Sci. U.S.A. 97 (2000) 9293-9298]. We find that while tunicamycin treatment had no effect on CaV2.2 current in the inactivation-sensitive isolated chick dorsal root ganglion (DRG) neuron, it caused a 10mV hyperpolarized shift in the profile of the inactivation-resistant presynaptic CaV2.2 population. This shift occurred without any effect on the voltage sensitivity of the inactivation process, as measured by a Boltzmann slope factor. Our findings suggest that dynamic palmitoylation contributes to the hyperpolarized steady inactivation profile of presynaptic CaV2.2. However, some other factor must also contribute since its inhibition does is not restore the inactivation profile to that of channels in the cell soma.
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PMID:Resistance of presynaptic CaV2.2 channels to voltage-dependent inactivation: dynamic palmitoylation and voltage sensitivity. 1760 41