Disease relevance of QX-222

• Nerve injury-induced tactile hypersensitivity, however, was reversed by systemic lidocaine but not QX-314 or QX-222 [1].

High impact information on QX-222

• The binding site for an open-channel blocker, QX-222, at mouse muscle nicotinic acetylcholine receptors was probed using site-directed mutagenesis, oocyte expression, and electrophysiological analysis [2].
• The proposed cytoplasmic end of the M2 transmembrane helix is termed position 1'. At position 10' (alpha S252, beta T263, gamma A261, delta A266), Ala residues yield stronger and longer binding of QX-222 than Ser or Thr residues [2].
• Spontaneous and evoked action potentials were blocked by TTX or by intracellular injection of a local anesthetic, QX-222 [3].
• We conclude that ether and QX-222 do not compete for a common binding site [4].
• We report measurement of the gating currents of Na channels in canine cardiac Purkinje cells in the absence and presence of QX-222, a quaternary derivative of lidocaine, applied intracellularly, and benzocaine, a neutral local anesthetic [5].

Biological context of QX-222

• 7. Raising QX-222 concentration, at any given membrane potential, augments I1(0) and I3(0) at the expense of I2(0) [6].
• It is hypothesized that the second component in QX-222 represents currents of unaltered or normal conductance kinetics, and that the first and third components in QX-222, as well as the major component and tail in QX-314, represent current of "QX-altered conductance kinetics" [6].
• Reversibility of Ia EPSP investigated with intracellularly iontophoresed QX-222 [7].
• 2 QX-222 and procaine, applied to the extracellular surface, reversibly inhibited the peak amplitude of the whole-cell nicotinic ACh-evoked current in a concentration-dependent manner, with half-maximal inhibitory concentrations (IC50) of 28 microM and 2.8 microM, respectively, at -80 mV [8].
• We have been examining the interaction of a local anesthetic derivative, QX-222, with the ion channel pore of the muscle AChR, using a combination of mutagenesis, oocyte expression, and electrophysiology [9].

Anatomical context of QX-222

• For Xenopus myocyte cholinergic receptors, examples of the use of this method are given for several concentration-dependent reactions including blockade by the local anesthetic QX-222, activation by acetylcholine, and modulation of current amplitude by sodium ions [10].

Associations of QX-222 with other chemical compounds

• The effects of intracellular applications of QX 222, a quaternary analogue of lidocaine, were investigated in CA1 neurons of in vitro hippocampal slices of guinea-pig brain [11].
• However, QX 222 also apparently interferes with the functions of Na+-channels activated by glutamate-receptor interaction or by receptor interactions with neurotransmitter(s) associated with certain excitatory postsynaptic potentials in CA1 neurons [11].

Analytical, diagnostic and therapeutic context of QX-222

• Both agents totally blocked AP generation without decreasing the magnitude of the Ia e.p.s.p. It is suggested that intracellularly iontophoresed QX-222 (on account of its low lipid solubility) could be used as a pharmacological tool to block specifically the active Na and channels in only the cell impaled by the microelectrodes [12].
• 3. Intracellular iontophoresis of QX-222 (a trimethyl analogue of lignocaine) or methylxylocholine, prevented action-potential generation and reduced the GM increase during current depolarization so that positive levels of EM could be reached [7].

References