6-cyano-7-nitroquinoxaline-2-3-dione and nickel-chloride

Active dendritic membrane properties were investigated by whole cell recordings from adult turtle olfactory bulb granule cells. The laminar structure of the olfactory bulb allowed differential polarization of the distal apical dendrites versus the somatic part of the cells by an external electric field. Dendritic depolarization evoked small (approximately 10 mV) all-or-none depolarizing events of approximately 10-ms duration. These spikelets often occurred in bursts at high frequency (< or = 250 Hz); they were present despite the application of synaptic and gap junction antagonists, but were abolished by TTX and intracellularly applied QX314. The spikelets were interpreted as attenuated sodium spikes initiated in different branches of the granule cells dendrites. They occurred spontaneously, but could also be evoked by excitatory postsynaptic potentials (EPSPs) to the distal dendrites. Spikelets initiated by distal excitation could function as prepotentials for full sodium spikes, in part depending on the level of proximal depolarization. Somatic depolarization by the electric field evoked full sodium spikes as well as low-threshold calcium spikes (LTSs). Calcium imaging revealed that the electrophysiologically identified LTS evoked from the soma was associated with calcium transients in the proximal and the distal dendrites. Our data suggest that the LTS in the soma/proximal dendrites plays a major role in boosting excitability, thus contributing to the initiation of sodium spiking in this compartment. The results furthermore suggest that the LTS and the sodium spikes may act independently or cooperatively to regulate dendritic calcium influx.

Topics: 6-Cyano-7-nitroquinoxaline-2,3-dione; Animals; Calcium; Calcium Channel Blockers; Dendrites; Diagnostic Imaging; Dose-Response Relationship, Radiation; Drug Interactions; Electric Stimulation; Evoked Potentials; Excitatory Amino Acid Agonists; Excitatory Amino Acid Antagonists; GABA Antagonists; In Vitro Techniques; Membrane Potentials; Mibefradil; Models, Neurological; Neurons; Nickel; Olfactory Bulb; Patch-Clamp Techniques; Pyridazines; Sodium; Synaptic Transmission; Tetrodotoxin; Time Factors; Turtles; Valine

Previously, we reported that Ca(2+) influx through nicotinic acetylcholine (ACh) receptors (nAChRs) activates a fulfenamic acid (FFA)-sensitive inward current, presumably a Ca(2+)-activated nonselective cation current (I(CAN)), in mesencephalic dopamine (DA) neurons. This current exhibited a negative slope conductance in the voltage range between -80 and -40mV and its activation led to a dramatic change in the responses to a transient application of glutamate, from single spikes to burst discharges. In this study, to examine the effect of activation of the FFA-sensitive current on EPSPs, we applied ACh (1mM) by transient air pressure shortly before electrical stimulation to evoke EPSPs in DA neurons. Application of ACh enhanced the amplitude of EPSPs when it preceded the electrical stimulation by less than 2 s, but not when the interval was longer than 3 s. In addition, this enhancement was critically dependent on intracellular Ca(2+) and the membrane potentials of the postsynaptic cell. Furthermore, the enhancing effect of ACh on EPSPs was sensitive to FFA and phenytoin. These results suggest that Ca(2+) influx caused by cholinergic inputs enhances EPSPs via activation of the FFA- and phenytoin-sensitive current.

Topics: 6-Cyano-7-nitroquinoxaline-2,3-dione; Acetylcholine; Animals; Animals, Newborn; Atropine; Chelating Agents; Dopamine; Drug Interactions; Egtazic Acid; Enzyme Inhibitors; Excitatory Amino Acid Antagonists; Excitatory Postsynaptic Potentials; In Vitro Techniques; Mesencephalon; Muscarinic Antagonists; Neurons; Nickel; ortho-Aminobenzoates; Patch-Clamp Techniques; Pertussis Toxin; Phenytoin; Rats; Thapsigargin; Time Factors; Valine

One-half of the subthalamic nucleus (STN) neurons switch from single-spike activity to burst-firing mode according to membrane potential. In an earlier study, the ionic mechanisms of the bursting mode were studied but the ionic currents underlying single-spike activity were not determined. The single-spike mode of activity of STN neurons recorded from acute slices in the current clamp mode is TTX-sensitive but is not abolished by antagonists of ionotropic glutamatergic and GABAergic receptors, blockers of calcium currents (2 mM cobalt or 40 microM nickel), or intracellular Ca(2+) ions chelators. Tonic activity is characterized by a pacemaker depolarization that spontaneously brings the membrane from the peak of the afterspike hyperpolarization (AHP) to firing threshold (from -57.1 +/- 0.5 mV to -42.2 +/- 0.3 mV). Voltage-clamp recordings suggest that the Ni(2+)-sensitive, T-type Ca(2+) current does not play a significant role in single-spike activity because it is totally inactivated at potentials more depolarized than -60 mV. In contrast, the TTX-sensitive, I(NaP) that activated at -54.4 +/- 0.6 mV fulfills the conditions for underlying pacemaker depolarization because it is activated below spike threshold and is not fully inactivated in the pacemaker range. In some cases, the depolarization required to reach the threshold for I(NaP) activation is mediated by hyperpolarization-activated cation current (I(h)). This was directly confirmed by the cesium-induced shift from single-spike to burst-firing mode which was observed in some STN neurons. Therefore, a fraction of I(h) which is tonically activated at rest, exerts a depolarizing influence and enables membrane potential to reach the threshold for I(NaP) activation, thus favoring the single-spike mode. The combined action of I(NaP) and I(h) is responsible for the dual mode of discharge of STN neurons.

Topics: 2-Amino-5-phosphonovalerate; 6-Cyano-7-nitroquinoxaline-2,3-dione; Action Potentials; Animals; Bicuculline; Biological Clocks; Calcium; Cesium; Chelating Agents; Egtazic Acid; Excitatory Amino Acid Antagonists; GABA Antagonists; Male; Neurons; Nickel; Patch-Clamp Techniques; Periodicity; Rats; Rats, Wistar; Sodium; Subthalamic Nucleus; Tetrodotoxin