- reversed use-dependent
- seek or achieve an end by using to ones advantage; "She uses her influential friends to get jobs"; "The presidents wife used her good connections"
- the act of using; "he warned against the use of narcotic drugs"; "skilled in the utilization of computers" (同)usage, utilization, utilisation, employment, exercise
- a particular service; "he put his knowledge to good use"; "patrons have their uses"
- (law) the exercise of the legal right to enjoy the benefits of owning property; "we were given the use of his boat" (同)enjoyment
- use up, consume fully; "The legislature expended its time on school questions" (同)expend
- take or consume (regularly or habitually); "She uses drugs rarely" (同)habituate
- put into service; make work or employ for a particular purpose or for its inherent or natural purpose; "use your head!"; "we only use Spanish at home"; "I cant use this tool"; "Apply a magnetic field here"; "This thinking was applied to many projects"; "How do you utilize this tool?"; "I apply this rule to get good results"; "use the plastic bags to store the food"; "He doesnt know how to use a computer" (同)utilize, utilise, apply, employ
- habitually do something (use only in the past tense); "She used to call her mother every week but now she calls only occasionally"; "I used to get sick when I ate in that dining hall"; "They used to vacation in the Bahamas"
- of the transmission gear causing backward movement in a motor vehicle; "in reverse gear"
- a relation of direct opposition; "we thought Sue was older than Bill but just the reverse was true" (同)contrary, opposite
- the gears by which the motion of a machine can be reversed (同)reverse gear
- the side of a coin or medal that does not bear the principal design (同)verso
- (American football) a running play in which a back running in one direction hands the ball to a back running in the opposite direction
- an unfortunate happening that hinders or impedes; something that is thwarting or frustrating (同)reversal, setback, blow, black_eye
- the state of relying on or being controlled by someone or something else (同)dependance, dependency
- a lapel on a womans garment; turned back to show the reverse side (同)revere
- 〈道具など〉‘を'『使う』,用いる / …‘を'『費す』,消費する / 《副詞[句]を伴って》〈人など〉‘を'『扱う』 / …‘を'自分の都合のいいように合用する / 〈U〉『使用』,利用 / 〈U〉『役に立つこと』,効用,利益(usefulness) / 〈U〉使う必要(場合),使用する機会,入り用 / 〈C〉〈U〉使用の目的,用途 / 〈U〉使用する権利 / 〈U〉使い方 / 〈U〉(身体などを)使う能力
- (位置・方向・順序などにおいて)『逆の』;裏側の』 / 逆に動かす(動く),バックの / 〈U〉《the reverse》(…の)『反対』,『逆』《+『of』+『名』(『wh』‐節)》》 / 〈U〉《the reverse》(貨幣・メダルなどの)『裏側』,(一般に)(…の)裏面《+『of』+『名』》 / 〈C〉(運命などの)逆転,不運 / 〈U〉後退[装置],逆転[装置] / …‘を'『逆にする』,反対にする;…‘を'裏返す / 〈機械など〉‘を'逆転させる,逆方向に動かす / 〈判決など〉‘を'取り消す,破棄する / (ダンスで)逆に回る / 〈機械などが〉逆方向に動く
- (…に)頼ること,(…への)依存,依頼《+『on(upon)』+『名』》 / (…への)信頼,信用《+『on』+『名』》
- 『…するのが常だった』,よく…したものだ / 『以前は…した』
全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.
- Scorpion β-toxin interference with NaV channel voltage sensor gives rise to excitatory and depressant modes.
- Leipold E1, Borges A, Heinemann SH.Author information 1Department of Biophysics, Center for Molecular Biomedicine, Friedrich Schiller University of Jena and Jena University Hospital, Jena D-07745, Germany.AbstractScorpion β toxins, peptides of ∼70 residues, specifically target voltage-gated sodium (Na(V)) channels to cause use-dependent subthreshold channel openings via a voltage-sensor trapping mechanism. This excitatory action is often overlaid by a not yet understood depressant mode in which Na(V) channel activity is inhibited. Here, we analyzed these two modes of gating modification by β-toxin Tz1 from Tityus zulianus on heterologously expressed Na(V)1.4 and Na(V)1.5 channels using the whole cell patch-clamp method. Tz1 facilitated the opening of Na(V)1.4 in a use-dependent manner and inhibited channel opening with a reversed use dependence. In contrast, the opening of Na(V)1.5 was exclusively inhibited without noticeable use dependence. Using chimeras of Na(V)1.4 and Na(V)1.5 channels, we demonstrated that gating modification by Tz1 depends on the specific structure of the voltage sensor in domain 2. Although residue G658 in Na(V)1.4 promotes the use-dependent transitions between Tz1 modification phenotypes, the equivalent residue in Na(V)1.5, N803, abolishes them. Gating charge neutralizations in the Na(V)1.4 domain 2 voltage sensor identified arginine residues at positions 663 and 669 as crucial for the outward and inward movement of this sensor, respectively. Our data support a model in which Tz1 can stabilize two conformations of the domain 2 voltage sensor: a preactivated outward position leading to Na(V) channels that open at subthreshold potentials, and a deactivated inward position preventing channels from opening. The results are best explained by a two-state voltage-sensor trapping model in that bound scorpion β toxin slows the activation as well as the deactivation kinetics of the voltage sensor in domain 2.
- The Journal of general physiology.J Gen Physiol.2012 Apr;139(4):305-19. doi: 10.1085/jgp.201110720.
- Scorpion β toxins, peptides of ∼70 residues, specifically target voltage-gated sodium (Na(V)) channels to cause use-dependent subthreshold channel openings via a voltage-sensor trapping mechanism. This excitatory action is often overlaid by a not yet understood depressant mode in which Na(V) chan
- PMID 22450487
- Merging Structural Motifs of Functionalized Amino Acids and α-Aminoamides Results in Novel Anticonvulsant Compounds with Significant Effects on Slow and Fast Inactivation of Voltage-gated Sodium Channels and in the Treatment of Neuropathic Pain.
- Wang Y1, Wilson SM, Brittain JM, Ripsch MS, Salomé C, Park KD, White FA, Khanna R, Kohn H.Author information 1Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, IN 46202.AbstractWe recently reported that merging key structural pharmacophores of the anticonvulsant drugs lacosamide (a functionalized amino acid) with safinamide (an α-aminoamide) resulted in novel compounds with anticonvulsant activities superior to that of either drug alone. Here, we examined the effects of six such chimeric compounds on Na(+)-channel function in central nervous system catecholaminergic (CAD) cells. Using whole-cell patch clamp electrophysiology, we demonstrated that these compounds affected Na(+) channel fast and slow inactivation processes. Detailed electrophysiological characterization of two of these chimeric compounds that contained either an oxymethylene ((R)-7) or a chemical bond ((R)-11) between the two aromatic rings showed comparable effects on slow inactivation, use-dependence of block, development of slow inactivation, and recovery of Na(+) channels from inactivation. Both compounds were equally effective at inducing slow inactivation; (R)-7 shifted the fast inactivation curve in the hyperpolarizing direction greater than (R)-11, suggesting that in the presence of (R)-7, a larger fraction of the channels are in an inactivated state. None of the chimeric compounds affected veratridine- or KCl-induced glutamate release in neonatal cortical neurons. There was modest inhibition of KCl-induced calcium influx in cortical neurons. Finally, a single intraperitoneal administration of (R)-7, but not (R)-11, completely reversed mechanical hypersensitivity in a tibial-nerve injury model of neuropathic pain. The strong effects of (R)-7 on slow and fast inactivation of Na(+) channels may contribute to its efficacy and provide a promising novel therapy for neuropathic pain, in addition to its antiepileptic potential.
- ACS chemical neuroscience.ACS Chem Neurosci.2011 Jun 15;2(6):317-322.
- We recently reported that merging key structural pharmacophores of the anticonvulsant drugs lacosamide (a functionalized amino acid) with safinamide (an α-aminoamide) resulted in novel compounds with anticonvulsant activities superior to that of either drug alone. Here, we examined the effects of s
- PMID 21765969
- Modulation of the hyperpolarisation-activated current, Ih, in rat facial motoneurones in vitro by ZD-7288.
- Larkman PM1, Kelly JS.Author information 1Department of Neuroscience, University of Edinburgh, 1 George Square, Edinburgh EH8 9JZ, Scotland, UK. email@example.comAbstractZD-7288 [4-(N-ethyl-N-phenylamino)-1,2-dimethyl-6-(methylamino) pyrimidinium chloride] and Cs(+) have been used to distinguish the currents contributing to inward rectification in neonatal rat facial motoneurones (FMs). ZD-7288 (0.1-10 microM) inhibited a current that reversed at -43.7+/-3.7 mV in artificial cerebrospinal fluid (ACSF) containing 3 mM K(+) (n=9), and displayed the time and voltage dependence of the hyperpolarisation-activated current, I(h). Depolarisation-activated transient (I(K(A))) and sustained outward currents were unaffected by ZD-7288. The IC(50) for block of I(h) by ZD-7288 was around 0.2 microM. Onset of inhibition was slow and no recovery was seen after washing in ZD-7288-free ACSF for up to 4 h. In the presence of ZD-7288, Ba(2+) and Rb(+) blocked an inwardly rectifying potassium (K(+)) current, confirming both the presence of I(K(IR)) and its insensitivity to ZD-7288. Cs(+) rapidly and reversibly blocked both I(h) and I(K(IR)). Inhibition of I(h) by ZD-7288 showed no use dependence, internally applied ZD-7288 also blocked I(h), and tail current analysis indicated inhibition to be voltage-independent. In the presence of internal guanosine 5'-O-(3-thiotriphosphate) (GTP-gamma-S) and after previous exposure to ZD-7288, 5-hydroxytryptamine (5-HT), but not noradrenaline, promoted a recovery of I(h) that was not observed if ZD-7288 was present throughout the recording period. This interaction between ZD-7288 and irreversible 5-HT-receptor activation may be related to the mechanism underlying ZD-7288-mediated block of these channels.
- Neuropharmacology.Neuropharmacology.2001 Jun;40(8):1058-72.
- ZD-7288 [4-(N-ethyl-N-phenylamino)-1,2-dimethyl-6-(methylamino) pyrimidinium chloride] and Cs(+) have been used to distinguish the currents contributing to inward rectification in neonatal rat facial motoneurones (FMs). ZD-7288 (0.1-10 microM) inhibited a current that reversed at -43.7+/-3.7 mV in a
- PMID 11406198
- 創薬における薬理学の役割 抗不整脈薬の新しい展開:創薬における薬理学の役割
- 菅野 盛夫
- 日本薬理学雑誌 102(3), 215-223, 1993
- … However, their reversed use-dependence of action potential duration prolonging effect contributes to their untoward action of proarrhythmias. …
- NAID 130000760109
- Class III antiarrhythmic agents exhibit reverse use dependent prolongation of the action potential duration (Reverse use-dependence). This means that the refractoriness of the ventricular myocyte increases at lower heart rates. This increases ...
- Basically they act on the cells and tissues that they are suppose to. Therefore their ability to work is dependent on the state of the tissue (active and/or inactive Na channels). Reverse use dependence is the exact opposite.
- reversed use-dependence、reversed use-dependent
- reversed use-dependence
- employ、employment、exploit、exploitation、harness、make use of、take advantage of、usage、utilisation、utilise、utilization、utilize