Disease relevance of QX 314

• 3. The quaternary derivatives QX-314 (0.1-1.0 mM) and QX-222 (0.3-3.0 mM) resulted in more complete recovery of the CAP area from anoxia, with less depression of preanoxic excitability, compared with the tertiary compounds [1].
• These data support the hypothesis that Na+ channel accumulation contributes to the generation of ectopic discharges in neuromas and DRG, and suggests that intravenous QX-314 can acutely block Na+ channels at these sites [2].
• Microinjection of either lidocaine or QX-314 into the rostral ventromedial medulla fully reversed spinal nerve ligation-induced thermal and tactile hypersensitivity [3].

High impact information on QX 314

• Comparison of effects of L and QX-314 after intracellular injection showed that attenuation of Vmax, and thus of the fast inward current, results from interaction of the charged form acting form acting from the inner surface of the sarcolemma [4].
• Residual spatial differences that persist in QX-314 experiments are consistent with the idea that VDCCs have decreased density on distal-apical dendrites [5].
• However, since similar degrees of EPSP potentiation were observed following blockade of spike activity by intracellular QX-314, spike activity was not the primary conditioning factor [6].
• Use-dependent Na+ channel blockers, particularly charged compounds such as QX-314, are highly neuroprotective in vitro, but only agents that exist partially in a neutral form, such as mexiletine and tocainide, are effective after systemic administration, because charged species cannot penetrate the blood-brain barrier easily [7].
• The level of block, for either period, at various QX-314 concentrations indicated the presence of a single local anesthetic binding site [8].

Chemical compound and disease context of QX 314

• Lidocaine or QX-314 also significantly reduced HR and MBP in the same dose range as that which reduced ENA in DRG or neuromas [2].

Biological context of QX 314

• 7. The SyPP was more sensitive than the large amplitude action potential to intracellular injection of QX-314, a lidocaine derivative [9].
• When evoked at less negative membrane potentials (i.e. -20 to -55 mV) after intracellular injection of Cs+ and QX-314, the EPSPs had a slow depolarizing potential, similar to the EPSPs from optic nerve stimulation.(ABSTRACT TRUNCATED AT 400 WORDS)[10]
• 4. weaver cerebellar granule cells could be rescued from cell death by the GIRK2wv cationic channel blocker, QX-314 [11].
• 2. Both QX-222 and QX-314, the trimethyl and triethyl analogues, respectively, of lidocaine, greatly modify end-plate current kinetics [12].
• In isolated rat vagus nerve recordings, QX-314 induced marked use-dependent inhibition of C-spike amplitude, with IC50 values (microM) of 9000 (4600-18,000) and 350 (290-420) for low- (0.03 Hz) and high-frequency (30 Hz) C-spikes, respectively [2].

Anatomical context of QX 314

• Anomalous inward rectification was depressed by QX-314 in somata but not in dendrites, suggesting that the ionic basis for subthreshold as well as regenerative conductances was different at different sites on the neuron [13].
• 5. Inhibitory p.s.p.s (i.p.s.p.s) were studied in depolarized pyramidal cells with microelectrodes filled with QX-314 [14].
• We have studied the block by lidocaine and its quaternary derivative, QX-314, of single, batrachotoxin (BTX)-activated cardiac and skeletal muscle sodium channels incorporated into planar lipid bilayers [15].
• Application of QX-314 (QX, 0-4 mM) to the cytoplasmic membrane surface caused two distinct modalities of single-channel blockade: reduction of unitary current and interruptions of current lasting tens of milliseconds [16].
• It was possible to induce oscillations in these neurones by the injection of depolarizing current (in the presence of QX-314), suggesting that these neurones are also gap-junction coupled [17].

Associations of QX 314 with other chemical compounds

• Alanine mutations in the extracellular half of the M2 transmembrane domain alter QX-314 inhibition, indicating the M2 forms part of the intrapore binding site [18].
• To selectively block the first or second phase, we respectively used remifentanil, a potent and short acting opiate agonist, and QX-314, a quaternary derivative of lidocaine, which does not cross the blood brain barrier [19].
• We conclude that the charge immobilization is restored by QX-314 in the chloramine-T-treated axon and that the gating state of the QX-314-bound channel is similar to the inactivated one [20].
• 5. To examine the effects of Saffan on electrotonic coupling between SPNs, experiments were performed with the Na+ channel blocker QX-314 in the intracellular solution and antidromic oscillations were evoked by ventral root stimulation [21].
• 5. Intracellular application of the lidocaine derivative N-(2,6-dimethyl-phenylcarbamoylmethyl) triethylammonium bromide (QX 314) at 100 mM from pipettes rapidly abolished fast action potentials and inward rectification [22].

Gene context of QX 314

• However, internally applied QX-314 (in the presence of external TTX) caused an immediate charge immobilization similar to that observed in the absence of CT treatment [20].
• The fast (Cl(-)-dependent, GABAA receptor-mediated) IPSPs (fIPSPs) were isolated from the slow (K(+)-dependent; GABAB receptor-mediated) IPSPs (sIPSPs) by intracellular injection of QX-314, which also suppressed fast (Na(+)-dependent) action potentials [23].
• Both mGluR slow potential and slow oscillation persisted in the presence of gabazine (10 microM), a GABA(A) receptor antagonist, and intracellular QX-314 (10 mM), a Na+ channel blocker [24].
• The presence of QX-314 in the CA1 neurons, which suppressed the Na+ spikes and the slow IPSPs, prevented the hyperpolarization of the neurons by somatostatin and baclofen.(ABSTRACT TRUNCATED AT 250 WORDS)[25]
• This constitutively activated conductance displayed a sensitivity to external QX-314 (IC(50) = 10.6 microM) very similar to that of heterologously expressed wvGirk2 channels and was not further activated by G-protein stimulation [26].

Analytical, diagnostic and therapeutic context of QX 314

• A voltage clamp technique was used to study sodium currents and gating currents in squid axons internally perfused with the membrane impermeant sodium channel blocker, QX-314 [27].
• Local blockade of peripheral activity by QX-314 at the amputated hindpaw 120 min after amputation did not significantly affect sensory responses induced within the ACC [28].
• EPSCs were evoked by local electrical stimulation, and all experiments were conducted in the presence of bicuculline methchloride in the bathing medium and with QX-314 in the recording pipette [29].
• In terms of their possible participation in theta rhythm genesis the slow QX-314-resistant events display the correct frequency and duration and can oscillate regeneratively [30].
• When bicuculline was present in the perfusion medium and following intracellular injection of QX 314, GABA(A) and GABA(B) receptors in the recorded neurons were blocked [31].

References