Complex Blockade of TTX-Resistant Na+ Currents by Lidocaine and Bupivacaine Reduce Firing Frequency in DRG Neurons

1998 ◽  
Vol 79 (4) ◽  
pp. 1746-1754 ◽  
Author(s):  
Andreas Scholz ◽  
Noboru Kuboyama ◽  
Gunter Hempelmann ◽  
Werner Vogel
Keyword(s):  
Spinal Anesthesia ◽  
Action Potentials ◽  
Sensory Information ◽  
Firing Frequency ◽  
Drg Neurons ◽  
Patch Clamp Technique ◽  
Single Action ◽  
Na Currents ◽  
Frequency Of Action Potentials ◽  
Frequency Of Stimulation

Scholz, Andreas, Noboru Kuboyama, Gunter Hempelmann, and Werner Vogel. Complex blockade of TTX-resistant Na+ currents by lidocaine and bupivacaine reduce firing frequency in DRG neurons. J. Neurophysiol. 79: 1746–1754, 1998. Mechanisms of blockade of tetrodotoxin-resistant (TTXr) Na+ channels by local anesthetics in comparison with the sensitivity of tetrodotoxin-sensitive (TTXs) Na+ channels were studied by means of the patch-clamp technique in neurons of dorsal root ganglions (DRG) of rat. Half-maximum inhibitory concentration (IC50) for the tonic block of TTXr Na+ currents by lidocaine was 210 μmol/l, whereas TTXs Na+ currents showed five times lower IC50 of 42 μmol/l. Bupivacaine blocked TTXr and TTXs Na+ currents more potently with IC50 of 32 and 13 μmol/l, respectively. In the inactivated state, TTXr Na+ channel block by lidocaine showed higher sensitivities (IC50 = 60 μmol/l) than in the resting state underlying tonic blockade. The time constant τ1 of recovery of TTXr Na+ channels from inactivation at −80 mV was slowed from 2 to 5 ms after addition of 10 μmol/l bupivacaine, whereas the τ2 value of ∼500 ms remained unchanged. The use-dependent block of TTXr Na+ channels led to a progressive reduction of current amplitudes with increasing frequency of stimulation, which was ≤53% block at 20 Hz in 10 μmol/l bupivacaine and 81% in 100 μmol lidocaine. The functional importance of the use-dependent block was confirmed in current-clamp experiments where 30 μmol/l of lidocaine or bupivacaine did not suppress the single action potential but clearly reduced the firing frequency of action potentials again with stronger potency of bupivacaine. Because it was found that TTXr Na+ channels predominantly occur in smaller sensory neurons, their blockade might underlie the suppression of the sensation of pain. Different sensitivities and varying proportions of TTXr and TTXs Na+ channels could explain the known differential block in spinal anesthesia. We suggest that the frequency reduction at low local anesthetic concentrations may explain the phenomenon of paresthesia where sensory information are suppressed gradually during spinal anesthesia.

scholarly journals Human Nav1.8: enhanced persistent and ramp currents contribute to distinct firing properties of human DRG neurons

2015 ◽  
Vol 113 (9) ◽  
pp. 3172-3185 ◽  
Author(s):  
Chongyang Han ◽  
Mark Estacion ◽  
Jianying Huang ◽  
Dymtro Vasylyev ◽  
Peng Zhao ◽  
...  
Keyword(s):  
Action Potentials ◽  
Firing Frequency ◽  
Inactivation Kinetics ◽  
Drg Neurons ◽  
Current Clamp ◽  
Single Action ◽  
Ion Channel Properties ◽  
Firing Properties ◽  
Species Specific ◽  
Channel Properties

Although species-specific differences in ion channel properties are well-documented, little has been known about the properties of the human Nav1.8 channel, an important contributor to pain signaling. Here we show, using techniques that include voltage clamp, current clamp, and dynamic clamp in dorsal root ganglion (DRG) neurons, that human Nav1.8 channels display slower inactivation kinetics and produce larger persistent current and ramp current than previously reported in other species. DRG neurons expressing human Nav1.8 channels unexpectedly produce significantly longer-lasting action potentials, including action potentials with half-widths in some cells >10 ms, and increased firing frequency compared with the narrower and usually single action potentials generated by DRG neurons expressing rat Nav1.8 channels. We also show that native human DRG neurons recapitulate these properties of Nav1.8 current and the long-lasting action potentials. Together, our results demonstrate strikingly distinct properties of human Nav1.8, which contribute to the firing properties of human DRG neurons.

scholarly journals Nicotine suppresses hyperexcitability of colonic sensory neurons and visceral hypersensivity in mouse model of colonic inflammation

2012 ◽  
Vol 302 (7) ◽  
pp. G740-G747 ◽  
Author(s):  
Galya R. Abdrakhmanova ◽  
Minho Kang ◽  
M. Imad Damaj ◽  
Hamid I. Akbarali
Keyword(s):  
Mouse Model ◽  
Action Potential ◽  
Action Potentials ◽  
Drg Neurons ◽  
Action Potential Firing ◽  
Colonic Inflammation ◽  
Single Action ◽  
Nicotine Administration ◽  
Potential Firing

Recently, we reported that nicotine in vitro at a low 1-μM concentration suppresses hyperexcitability of colonic dorsal root ganglia (DRG; L1-L2) neurons in the dextran sodium sulfate (DSS)-induced mouse model of acute colonic inflammation ( 1 ). Here we show that multiple action potential firing in colonic DRG neurons persisted at least for 3 wk post-DSS administration while the inflammatory signs were diminished. Similar to that in DSS-induced acute colitis, bath-applied nicotine (1 μM) gradually reduced regenerative multiple-spike action potentials in colonic DRG neurons to a single action potential in 3 wk post-DSS neurons. Nicotine (1 μM) shifted the activation curve for tetrodotoxin (TTX)-resistant sodium currents in inflamed colonic DRG neurons (voltage of half-activation changed from −37 to −32 mV) but did not affect TTX-sensitive currents in control colonic DRG neurons. Further, subcutaneous nicotine administration (2 mg/kg b.i.d.) in DSS-treated C57Bl/J6 male mice resulted in suppression of hyperexcitability of colonic DRG (L1-L2) neurons and the number of abdominal constrictions in response to intraperitoneal injection of 0.6% acetic acid. Collectively, the data suggest that neuronal nicotinic acetylcholine receptor-mediated suppression of hyperexcitability of colonic DRG neurons attenuates reduction of visceral hypersensitivity in DSS mouse model of colonic inflammation.

Low-Voltage-Activated Calcium Current Does Not Regulate the Firing Behavior in Paired Mechanosensory Neurons With Different Adaptation Properties

2000 ◽  
Vol 83 (2) ◽  
pp. 746-753 ◽  
Author(s):  
Shin-Ichi Sekizawa ◽  
Andrew S. French ◽  
Päivi H. Torkkeli
Keyword(s):  
Action Potential ◽  
Action Potentials ◽  
Low Voltage ◽  
Firing Frequency ◽  
Oscillatory Behavior ◽  
Firing Behavior ◽  
Single Action ◽  
Synaptic Excitation ◽  
Intracellular Ca ◽  
The Difference

Low-voltage-activated Ca2+ currents (LVA- I Ca) are believed to perform several roles in neurons such as lowering the threshold for action potentials, promoting burst firing and oscillatory behavior, and enhancing synaptic excitation. They also may allow rapid increases in intracellular Ca2+ concentration. We discovered LVA- I Ca in both members of paired mechanoreceptor neurons in a spider, where one neuron adapts rapidly (Type A) and the other slowly (Type B) in response to a step stimulus. To learn if I Ca contributed to the difference in adaptation behavior, we studied the kinetics of I Ca from isolated somata under single-electrode voltage-clamp and tested its physiological function under current clamp. LVA- I Ca was large enough to fire single action potentials when all other voltage-activated currents were blocked, but we found no evidence that it regulated firing behavior. LVA- I Ca did not lower the action potential threshold or affect firing frequency. Previous experiments have failed to find Ca2+-activated K+ current ( I K(Ca)) in the somata of these neurons, so it is also unlikely that LVA- I Ca interacts with I K(Ca) to produce oscillatory behavior. We conclude that LVA-Ca2+ channels in the somata, and possible in the dendrites, of these neurons open in response to the depolarization caused by receptor current and by the voltage-activated Na+ current ( I Na) that produces action potential(s). However, the role of the increased intracellular Ca2+ concentration in neuronal function remains enigmatic.

Active contraction of nerve bundle and identification of a nerve-contractor motoneuron in Aplysia

1987 ◽  
Vol 58 (5) ◽  
pp. 1016-1034 ◽  
Author(s):  
Y. Umitsu ◽  
H. Matsumoto ◽  
H. Koike
Keyword(s):  
Cell Body ◽  
Action Potentials ◽  
Firing Frequency ◽  
Abdominal Ganglion ◽  
Dependent Manner ◽  
Antidromic Activation ◽  
Single Action ◽  
Active Contraction ◽  
Spike Triggered Averaging ◽  
Sensitive Marker

1. The active contraction or shortening of the nerves of Aplysia kurodai and Aplysia juliana was examined. 2. A particular neuron in the abdominal ganglion controlled the contractions of the nerves, and the neuron was identified as a gill- and siphon-contractor motoneuron previously identified as L7. This was based on the following observations, which agreed closely with those reported for L7: the position, shape, and color of the cell body of the neuron; the synaptic and antidromic activation of the neuron by stimulation of various nerves; and the configurations of the major axons as revealed by dye injection into the soma of the neuron. Finally, the activation of the neuron contracted the gill, and the characteristics of the contraction were those reported for L7. 3. L7 was the only neuron we could find in the abdominal ganglion that directly controlled the contractions of the nerves. This was supported by the following observations: 1) direct or synaptic activation of L7 made the nerves shorter in a firing frequency-dependent manner. 2) Even single action potentials of L7 contracted the nerves. 3) When L7 was destroyed, no contractions of the nerves were observed however strongly a stimulation was applied. 4) When every synaptic connection in the abdominal ganglion was blocked by bathing the ganglion in Cafree artificial seawater, direct or spontaneous activation of L7 still made the nerves shorter. 4. A sensitive marker, cobaltic-lysine complex solution, was injected into the cell body of L7, and many fine axonal branches were newly found in the epineurium of the nerves. With the use of spike-triggered averaging, small potentials were recorded from the contracting nerves. This suggested that the action potentials were conducted along the newly found fine branches of the axon to innervate the epineurial muscles. 5. We found that L7 is a multifunctional motoneuron that contracts nerves.

Electrogenic pump and a Ca(2+)- dependent K+ conductance contribute to a posttetanic hyperpolarization in lamprey sensory neurons

1996 ◽  
Vol 76 (1) ◽  
pp. 540-553 ◽  
Author(s):  
D. Parker ◽  
R. Hill ◽  
S. Grillner
Keyword(s):  
Action Potentials ◽  
Sensory Information ◽  
Input Resistance ◽  
Ringer Solution ◽  
K Channel ◽  
Electrogenic Pump ◽  
Gamma Aminobutyric Acid ◽  
Single Action ◽  
Biphasic Effect ◽  
Dorsal Cells

1. Tetanic stimulation of lamprey sensory dorsal cells resulted in a posttetanic hyperpolarization (PTH). The amplitude and duration of the PTH were dependent on the stimulus duration and frequency. The PTH was not reversed at membrane potentials negative to -100 mV, whereas the afterhyperpolarization following single action potentials reversed at approximately -85 mV. There was also a biphasic effect on the input resistance during the PTH, with an early reduction that recovered to control before the PTH had decayed. 2. The amplitude and duration of the PTH were increased in Ringer solution containing tetraethylammonium and 4-aminopyridine, both of which broadened single action potentials, but were reduced after intracellular injection of Cs+. Ca(2+)-free Ringer solution, Cd2+, and Co2+ also reduced the PTH, suggesting the involvement of a Ca(2+)-dependent K+ conductance. However, the PTH was not reduced in Ba2+ Ringer solution, or by the Ca(2+)-dependent K+ channel antagonists apamin and charybdotoxin. 3. The cardiac glycoside ouabain reduced the amplitude and duration of the PTH, as did substitution of Na+ with choline or Li+. K(+)-free Ringer solution also reduced the PTH, whereas high-K+ Ringer solution had more variable effects. The amplitude and duration of the PTH were also dependent on temperature. These results support the involvement of an ouabain-sensitive Na-K pump in the PTH. 4. The PTH was reduced by the tachykinins substance P and physalaemin, and by 5-hydroxytryptamine, which blocks apamin-sensitive Ca(2+)-dependent K+ channels in the lamprey. However, gamma-aminobutyric acid, which has been reported to reduce a Ca(2+)-dependent K+ conductance in the dorsal cells, did not reduce the PTH. 5. These results suggest that a Ca(2+)-dependent K+ conductance and an Na-K electrogenic pump underlie the PTH. The PTH reduces the excitability of the dorsal cells, suggesting that it may act as a mechanism to gate sensory information entering the spinal cord.

scholarly journals Distinct dendritic Ca2+ spike forms produce opposing input-output transformations in rat CA3 pyramidal cells

2021 ◽  
Author(s):  
Ádám Magó ◽  
Noémi Kis ◽  
Balázs Lükó ◽  
Judit K Makara
Keyword(s):  
Action Potentials ◽  
Dendritic Structure ◽  
Dendritic Tree ◽  
Pyramidal Cells ◽  
Afferent Input ◽  
Male Rats ◽  
Input Output ◽  
Single Action ◽  
Na Currents ◽  
Ca3 Pyramidal Cells

Proper integration of different inputs targeting the dendritic tree of CA3 pyramidal cells (CA3PCs) is critical for associative learning and recall. Dendritic Ca2+ spikes have been proposed to perform associative computations in other PC types, by detecting conjunctive activation of different afferent input pathways, initiating afterdepolarization (ADP) and triggering burst firing. Implementation of such operations fundamentally depends on the actual biophysical properties of dendritic Ca2+ spikes; yet little is known about these properties in dendrites of CA3PCs. Using dendritic patch-clamp recordings and two-photon Ca2+ imaging in acute slices from male rats we report that, unlike CA1PCs, distal apical trunk dendrites of CA3PCs exhibit distinct forms of dendritic Ca2+ spikes. Besides ADP-type global Ca2+ spikes, a majority of dendrites expresses a novel, fast Ca2+ spike type that is initiated locally without backpropagating action potentials, can recruit additional Na+ currents, and is compartmentalized to the activated dendritic subtree. Occurrence of the different Ca2+ spike types correlates with dendritic structure, indicating morpho-functional heterogeneity among CA3PCs. Importantly, ADPs and dendritically initiated spikes produce opposing somatic output: bursts versus strictly single action potentials, respectively. The uncovered variability of dendritic Ca2+ spikes may underlie heterogeneous input-output transformation and bursting properties of CA3PCs, and might specifically contribute to key associative and non-associative computations performed by the CA3 network.

scholarly journals Voltage-activated currents in guinea pig pancreatic alpha 2 cells. Evidence for Ca2+-dependent action potentials.

1988 ◽  
Vol 91 (2) ◽  
pp. 223-242 ◽  
Author(s):  
P Rorsman ◽  
B Hellman
Keyword(s):  
Guinea Pig ◽  
Action Potentials ◽  
Na Current ◽  
Patch Clamp Technique ◽  
Absolute Requirement ◽  
Na Currents ◽  
Electrophysiological Studies ◽  
Steady State Inactivation ◽  
Maximal Peak ◽  
K Current

Glucagon-secreting alpha 2 cells were isolated from guinea pig pancreatic islets and used for electrophysiological studies of voltage-activated ionic conductances using the patch-clamp technique. The alpha 2 cells differed from beta cells in producing action potentials in the absence of glucose. The frequency of these potentials increased after addition of 10 mM arginine but remained unaffected in the presence of 5-20 mM glucose. When studying the conductances underlying the action potentials, we identified a delayed rectifying K+ current, an Na+ current, and a Ca2+ current. The K+ current activated above -20 mV and then increased with the applied voltage. The Na+ current developed at potentials above -50 mV and reached a maximal peak amplitude of 550 pA during depolarizing pulses to -15 mV. The Na+ current inactivated rapidly (tau h approximately 0.7 ms at 0 mV). Half-maximal steady state inactivation was attained at -58 mV, and currents could no longer be elicited after conditioning pulses to potentials above -40 mV. The Ca2+ current first became detectable at -50 mV and reached a maximal amplitude of 90 pA (in extracellular [Ca2+] = 2.6 mM) at about -10 mV. Unlike the Na+ current, it inactivated little or not at all. Membrane potential measurements demonstrated that both the Ca2+ and Na+ currents contribute to the generation of the action potential. Whereas there was an absolute requirement of extracellular Ca2+ for action potentials to be elicited at all, suppression of the much larger Na+ current only reduced the upstroke velocity of the spikes. It is suggested that this behavior reflects the participation of a low-threshold Ca2+ conductance in the pacemaking of alpha 2 cells.

Calcium Dynamics and Compartmentalization in Leech Neurons

2005 ◽  
Vol 94 (6) ◽  
pp. 4430-4440 ◽  
Author(s):  
Sofija Andjelic ◽  
Vincent Torre
Keyword(s):  
Information Processing ◽  
Action Potential ◽  
Action Potentials ◽  
Time Course ◽  
Ccd Camera ◽  
Calcium Dynamics ◽  
Single Action ◽  
Single Action Potential ◽  
Calcium Indicator ◽  
Mechanosensory Neurons

Calcium dynamics in leech neurons were studied using a fast CCD camera. Fluorescence changes (Δ F/ F) of the membrane impermeable calcium indicator Oregon Green were measured. The dye was pressure injected into the soma of neurons under investigation. Δ F/ F caused by a single action potential (AP) in mechanosensory neurons had approximately the same amplitude and time course in the soma and in distal processes. By contrast, in other neurons such as the Anterior Pagoda neuron, the Annulus Erector motoneuron, the L motoneuron, and other motoneurons, APs evoked by passing depolarizing current in the soma produced much larger fluorescence changes in distal processes than in the soma. When APs were evoked by stimulating one distal axon through the root, Δ F/ F was large in all distal processes but very small in the soma. Our results show a clear compartmentalization of calcium dynamics in most leech neurons in which the soma does not give propagating action potentials. In such cells, the soma, while not excitable, can affect information processing by modulating the sites of origin and conduction of AP propagation in distal excitable processes.

Single-unit analysis of different hippocampal cell types during classical conditioning of rabbit nictitating membrane response

1983 ◽  
Vol 50 (5) ◽  
pp. 1197-1219 ◽  
Author(s):  
T. W. Berger ◽  
P. C. Rinaldi ◽  
D. J. Weisz ◽  
R. F. Thompson
Keyword(s):  
Classical Conditioning ◽  
Pyramidal Cell ◽  
Action Potentials ◽  
Pyramidal Cells ◽  
Cell Types ◽  
Firing Frequency ◽  
Spontaneous Firing ◽  
Nictitating Membrane ◽  
Nictitating Membrane Response ◽  
Firing Characteristics

Extracellular single-unit recordings from neurons in the CA1 and CA3 regions of the dorsal hippocampus were monitored during classical conditioning of the rabbit nictitating membrane response. Neurons were classified as different cell types using response to fornix stimulation (i.e., antidromic or orthodromic activation) and spontaneous firing characteristics as criteria. Results showed that hippocampal pyramidal neurons exhibit learning-related neural plasticity that develops gradually over the course of classical conditioning. The learning-dependent pyramidal cell response is characterized by an increase in frequency of firing within conditioning trials and a within-trial pattern of discharge that correlates strongly with amplitude-time course of the behavioral response. In contrast, pyramidal cell activity recorded from control animals given unpaired presentations of the conditioned and unconditioned stimulus (CS and UCS) does not show enhanced discharge rates with repeated stimulation. Previous studies of hippocampal cellular electrophysiology have described what has been termed a theta-cell (19-21, 45), the activity of which correlates with slow-wave theta rhythm generated in the hippocampus. Neurons classified as theta-cells in the present study exhibit responses during conditioning that are distinctly different than pyramidal cells. theta-Cells respond during paired conditioning trials with a rhythmic bursting; the between-burst interval occurs at or near 8 Hz. In addition, two different types of theta-cells were distinguishable. One type of theta-cell increases firing frequency above pretrial levels while displaying the theta bursting pattern. The other type decreases firing frequency below pretrial rates while showing a theta-locked discharge. In addition to pyramidal and theta-neurons, several other cell types recorded in or near the pyramidal cell layer could be distinguished. One cell type was distinctive in that it could be activated with a short, invariant latency following fornix stimulation, but spontaneous action potentials of such neurons could not be collided with fornix shock-induced action potentials. These neurons exhibit a different profile of spontaneous firing characteristics than those of antidromically identified pyramidal cells. Nevertheless, neurons in this noncollidable category display the same learning-dependent response as pyramidal cells. It is suggested that the noncollidable neurons represent a subpopulation of pyramidal cells that do not project an axon via the fornix but project, instead, to other limbic cortical regions.(ABSTRACT TRUNCATED AT 400 WORDS)

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