QX 314 bromide

Intracellular QX-314 blocks the hyperpolarization-activated inward current Iq in hippocampal CA1 pyramidal cells.[Pubmed:7760149]

J Neurophysiol. 1995 Feb;73(2):911-5.

1. Whole cell voltage-clamp recordings (access resistance < or = 12 M omega) from CA1 pyramidal cells in the guinea pig hippocampal slice revealed a hyperpolarization-activated inward current with an inward tail upon repolarization. The current activation range extended from approximately -50 mV to -130 mV, with half-activation at -86 mV. This current was identified as the q current (Iq). 2. Intracellular QX-314 (5 or 10 mM), a quaternary derivative of lidocaine, blocked Iq completely throughout its activation range. 3. There is a growing realization that Iq may be responsible for the pacemaker depolarization in cells that display rhythmic calcium spikes. Because QX-314 blocks Iq completely, it could be used to test whether Iq is essential to this oscillatory activity.

QX-314 blocks the potassium but not the sodium-dependent component of the opiate response in locus coeruleus neurons.[Pubmed:8205485]

Brain Res. 1994 Mar 14;639(2):320-4.

Opiates hyperpolarize locus coeruleus neurons by simultaneously opening K+ channels and turning off a resting Na(+)-dependent inward current. Intracellularly applied QX-314 reduced the opiate current to approximately 40% of the control and the residual current did not reverse near EK, suggesting lack of a significant K+ component. Replacement of Na+ virtually abolished the residual opiate response. Thus, QX-314 blocks the K+ but not the Na(+)-dependent component of the opiate-induced outward current in LC neurons.

The inhibition of sodium currents in myelinated nerve by quaternary derivatives of lidocaine.[Pubmed:4541340]

J Gen Physiol. 1973 Jul;62(1):37-57.

The inhibition of sodium currents by quaternary derivatives of lidocaine was studied in single myelinated nerve fibers. Membrane currents were diminished little by external quaternary lidocaine (QX). QX present in the axoplasm (<0.5 mM) inhibited sodium currents by more than 90%. Inhibition occurred as the sum of a constant, tonic phase and a variable, voltage-sensitive phase. The voltage-sensitive inhibition was favored by the application of membrane potential patterns which produce large depolarizations when sodium channels are open. Voltage-sensitive inhibition could be reversed by small depolarizations which opened sodium channels. One explanation of this observation is that QX molecules enter open sodium channels from the axoplasmic side and bind within the channels. The voltage dependence of the inhibition by QX suggests that the drug binds at a site which is about halfway down the electrical gradient from inside to outside of the sodium channel.

Intracellular QX-314 inhibits calcium currents in hippocampal CA1 pyramidal neurons.[Pubmed:8890325]

J Neurophysiol. 1996 Sep;76(3):2120-4.

1. The effects of intracellular QX-314 on Ca2+ currents were examined in CA1 pyramidal cells acutely isolated from rat hippocampus. In neurons dialyzed with 10 mM QX-314 (bromide salt), the amplitude of the high-threshold Ca2+ current was on average 20% of that in control cells and the current-voltage relationships (I-Vs) were shifted in the positive voltage direction. 2. The positive shift in the I-Vs was due to the presence of intracellular Br-, because it was reproduced by 10 mM NaBr and was not present when the chloride salt of QX-314 was used. 3. Low-threshold (T-type) Ca2+ currents, at test voltages of -50 and -40 mV, were on average < 45% of control amplitude in cells containing 10 mM QX-314 (chloride salt) and < 10% of control amplitude in cells with 10 mM QX-314 (bromide salt). 4. In neurons dialyzed with 1 mM QX-314, high-threshold Ca2+ currents were still significantly different from control and Na+ currents were not completely blocked. 5. The proportions of high-threshold Ca2+ current blocked by omega-conotoxin GVIA, omega-agatoxin IVA, and nimodipine were similar in cells dialyzed with 10 mM QX-314 and control cells, indicating that the drug does not selectively inhibit any of the Ca2+ channel subtypes distinguished by these antagonists.