Contribution of Nav1.8 Sodium Channels to Action Potential Electrogenesis in DRG Neurons

2001 ◽  
Vol 86 (2) ◽  
pp. 629-640 ◽  
Author(s):  
Muthukrishnan Renganathan ◽  
Theodore R. Cummins ◽  
Stephen G. Waxman
Keyword(s):  
Action Potential ◽  
Sodium Channels ◽  
Action Potentials ◽  
Input Resistance ◽  
Resting Membrane Potential ◽  
Drg Neurons ◽  
Significant Difference ◽  
Steady State Inactivation ◽  
Current Threshold

C-type dorsal root ganglion (DRG) neurons can generate tetrodotoxin-resistant (TTX-R) sodium-dependent action potentials. However, multiple sodium channels are expressed in these neurons, and the molecular identity of the TTX-R sodium channels that contribute to action potential production in these neurons has not been established. In this study, we used current-clamp recordings to compare action potential electrogenesis in Nav1.8 (+/+) and (−/−) small DRG neurons maintained for 2–8 h in vitro to examine the role of sodium channel Nav1.8 (α-SNS) in action potential electrogenesis. Although there was no significant difference in resting membrane potential, input resistance, current threshold, or voltage threshold in Nav1.8 (+/+) and (−/−) DRG neurons, there were significant differences in action potential electrogenesis. Most Nav1.8 (+/+) neurons generate all-or-none action potentials, whereas most of Nav1.8 (−/−) neurons produce smaller graded responses. The peak of the response was significantly reduced in Nav1.8 (−/−) neurons [31.5 ± 2.2 (SE) mV] compared with Nav1.8 (+/+) neurons (55.0 ± 4.3 mV). The maximum rise slope was 84.7 ± 11.2 mV/ms in Nav1.8 (+/+) neurons, significantly faster than in Nav1.8 (−/−) neurons where it was 47.2 ± 1.3 mV/ms. Calculations based on the action potential overshoot in Nav1.8 (+/+) and (−/−) neurons, following blockade of Ca2+ currents, indicate that Nav1.8 contributes a substantial fraction (80–90%) of the inward membrane current that flows during the rising phase of the action potential. We found that fast TTX-sensitive Na+ channels can produce all-or-none action potentials in some Nav1.8 (−/−) neurons but, presumably as a result of steady-state inactivation of these channels, electrogenesis in Nav1.8 (−/−) neurons is more sensitive to membrane depolarization than in Nav1.8 (+/+) neurons, and, in the absence of Nav1.8, is attenuated with even modest depolarization. These observations indicate that Nav1.8 contributes substantially to action potential electrogenesis in C-type 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.

scholarly journals Dopamine Increases Excitability of Pyramidal Neurons in Primate Prefrontal Cortex

2000 ◽  
Vol 84 (6) ◽  
pp. 2799-2809 ◽  
Author(s):  
Darrell A. Henze ◽  
Guillermo R. González-Burgos ◽  
Nathaniel N. Urban ◽  
David A. Lewis ◽  
German Barrionuevo
Keyword(s):  
Prefrontal Cortex ◽  
Action Potential ◽  
Pyramidal Neurons ◽  
Pyramidal Cells ◽  
Input Resistance ◽  
Initiation Site ◽  
D1 Receptor ◽  
Resting Membrane Potential ◽  
Cellular Mechanisms

Dopaminergic modulation of neuronal networks in the dorsolateral prefrontal cortex (PFC) is believed to play an important role in information processing during working memory tasks in both humans and nonhuman primates. To understand the basic cellular mechanisms that underlie these actions of dopamine (DA), we have investigated the influence of DA on the cellular properties of layer 3 pyramidal cells in area 46 of the macaque monkey PFC. Intracellular voltage recordings were obtained with sharp and whole cell patch-clamp electrodes in a PFC brain-slice preparation. All of the recorded neurons in layer 3 ( n = 86) exhibited regular spiking firing properties consistent with those of pyramidal neurons. We found that DA had no significant effects on resting membrane potential or input resistance of these cells. However DA, at concentrations as low as 0.5 μM, increased the excitability of PFC cells in response to depolarizing current steps injected at the soma. Enhanced excitability was associated with a hyperpolarizing shift in action potential threshold and a decreased first interspike interval. These effects required activation of D1-like but not D2-like receptors since they were inhibited by the D1 receptor antagonist SCH23390 (3 μM) but not significantly altered by the D2 antagonist sulpiride (2.5 μM). These results show, for the first time, that DA modulates the activity of layer 3 pyramidal neurons in area 46 of monkey dorsolateral PFC in vitro. Furthermore the results suggest that, by means of these effects alone, DA modulation would generally enhance the response of PFC pyramidal neurons to excitatory currents that reach the action potential initiation site.

Electrophysiological properties of neurons in the lateral habenula nucleus: an in vitro study

1988 ◽  
Vol 59 (1) ◽  
pp. 212-225 ◽  
Author(s):  
K. S. Wilcox ◽  
M. J. Gutnick ◽  
G. R. Christoph
Keyword(s):  
Membrane Potential ◽  
Action Potentials ◽  
In Vitro Study ◽  
Input Resistance ◽  
Membrane Potentials ◽  
Resting Membrane Potential ◽  
Lateral Habenula ◽  
Low Threshold ◽  
The Mean

1. The electroresponsive characteristics of neurons in the lateral habenula were studied with intracellular recordings in a brain slice preparation of guinea pig diencephalon maintained in vitro. One hundred and two neurons met the criteria for recording stability, and of these, 18 were analyzed in detail. For these 18 neurons, the mean resting membrane potential was -61.9 mV, the mean input resistance was 124 M omega, and the mean spike amplitude of fast action potentials was 60.3 mV. 2. Lateral habenula neurons were found to have distinct patterns of activity dependent on membrane potential. At membrane potentials more positive than -65 mV, depolarization elicited trains of sodium-dependent fast action potentials. At membrane potentials more negative than -65 mV, slight depolarization elicited a tetrodotoxin-insensitive wave of depolarization, called a low-threshold spike (LTS), from which a burst of fast action potentials were triggered. The principal conductance underlying the LTS is a low-threshold calcium conductance, which is inactivated at membrane potential more positive than -65 mV and deinactivated when the membrane is hyperpolarized to potentials more negative than -65 V. 3. Upon termination of injected hyperpolarizing current, many neurons displayed oscillation in membrane potential at a frequency of 3–10 Hz, thereby generating repetitive bursts of fast spikes. 4. The pattern of neuronal activity in lateral habenula neurons was highly sensitive to slight alterations in membrane potential. The ability of these neurons to fire action potentials in two modes, tonically and in bursts, and the propensity of these neurons to dramatically alter their output in response to transient hyperpolarizing input, indicate that transmission through this relay in the dorsal diencephalic conduction system may be greatly augmented by relatively small hyperpolarizing influences on the individual neurons.

Effect of enkephalins on colonic mechanoreceptor synaptic input to inferior mesenteric ganglion

1987 ◽  
Vol 252 (1) ◽  
pp. G128-G135 ◽  
Author(s):  
H. D. Shu ◽  
J. A. Love ◽  
J. H. Szurszewski
Keyword(s):  
Synaptic Input ◽  
Action Potentials ◽  
Input Resistance ◽  
Inhibitory Neurons ◽  
Intraluminal Pressure ◽  
Resting Membrane Potential ◽  
Inferior Mesenteric Ganglion ◽  
Mesenteric Ganglion ◽  
In Vitro Superfusion

The effects of leucine-enkephalin (Leu-Enk) on colonic mechanoreceptor input to the inferior mesenteric ganglion (IMG) and on colonic intraluminal pressure of the guinea pig were studied in vitro. Superfusion of the IMG with Leu-Enk decreased colonic, afferent mechanoreceptor synaptic input. In neurons in which mechanoreceptor input caused postsynaptic spikes, Leu-Enk decreased synaptic input and increased the basal intraluminal pressure of the colon. When mechanoreceptor input consisted of singly occurring excitatory postsynaptic potentials (EPSPs), Leu-Enk decreased the frequency of EPSPs but did not cause a change in colonic pressure. The inhibitory effects of Leu-Enk on synaptic transmission were antagonized by naloxone. In the isolated IMG, Leu-Enk converted synchronous action potentials in response to electrical stimulation of intermesenteric nerves to subthreshold EPSPs without a change in the resting membrane potential or input resistance. Action potentials elicited by depolarizing current pulses or by exogenous acetylcholine were unaltered by Leu-Enk. These data suggest that Leu-Enk increased colonic intraluminal pressure by acting on the presynaptic terminals of colonic mechanoreceptive neurons to reduce synaptic input to and output from the inhibitory neurons of the IMG.

TNBS ileitis evokes hyperexcitability and changes in ionic membrane properties of nociceptive DRG neurons

2002 ◽  
Vol 282 (6) ◽  
pp. G1045-G1051 ◽  
Author(s):  
Beverley A. Moore ◽  
Timothy M. R. Stewart ◽  
Ceredwyn Hill ◽  
Stephen J. Vanner
Keyword(s):  
Action Potential ◽  
Intestinal Inflammation ◽  
Input Resistance ◽  
Membrane Properties ◽  
Resting Membrane Potential ◽  
Cell Diameter ◽  
Trinitrobenzene Sulfonic Acid ◽  
Drg Neurons ◽  
Nociceptive Neurons ◽  
Electrophysiological Properties

This study examines whether intestinal inflammation leads to changes in the properties of ion channels in dorsal root ganglia (DRG) neurons. Ileitis was induced by injection of trinitrobenzene sulfonic acid (TNBS), and DRG neurons innervating the ileum were labeled using fast blue. Intracellular recording techniques were used to measure electrophysiological properties of acutely dissociated neurons 12–24 h after dissection. Nociceptive neurons were identified by sensitivity to capsaicin, tetrodotoxin resistance, and size (<30 μm). The action potential threshold in neurons from TNBS-treated animals was reduced by >70% compared with controls ( P < 0.001), but the resting membrane potential was unchanged. Cell diameter, input resistance (67%), and action potential upstroke velocity (22%) increased in the TNBS group ( P < 0.05). The number of action potentials discharged increased in the TNBS group ( P < 0.001), whereas application of 4-aminopyridine to control cells mimicked this effect. This study demonstrates that ileitis induces hyperexcitability in nociceptive DRG neurons and changes in the properties of Na+ and K+channels at the soma, which persist after removal from the inflamed environment.

Suppressive effect of acetylcholine on action potentials of canine paranodal fibers

1986 ◽  
Vol 251 (4) ◽  
pp. H710-H715
Author(s):  
W. W. Tse
Keyword(s):  
Membrane Potential ◽  
Action Potential ◽  
Action Potential Duration ◽  
Action Potentials ◽  
Conduction Block ◽  
Suppressive Effect ◽  
Resting Membrane Potential ◽  
Av Conduction ◽  
Av Conduction Block

The canine atrioventricular (AV) junction comprises three major tissues: paranodal fibers (PNF), AV node (AVN), and His bundle (HB). In the present study, dissection-exposed, in vitro canine AV junctional preparations were used. The object of the study was to determine whether the PNF or AVN was more sensitive to the suppressive effect of acetylcholine (ACh). In five experiments these tissues were stimulated antegradely and retrogradely, and their action potentials were recorded simultaneously under the influence of ACh (0.5 micrograms/ml). Results indicated the PNF were more sensitive to the suppressive effect of ACh than were the AVN. In another group of 13 experiments, the effects of ACh at 0.05-0.3 micrograms/ml on rate of rise of phase 0 of action potentials (Vmax), peak potential, resting membrane potential, and action potential duration of the PNF were determined. Results indicated that ACh exerted a strong suppressive effect on Vmax and amplitude of the action potentials and had little effect on the resting membrane potential and action potential duration of the PNF. In 10 of 13 preparations, ACh also suppressed the response of PNF, resulting in generation of one action potential to every two stimuli. In conclusion, these findings suggest that PNF could be the tissue responsible for vagal-induced AV conduction block.

Electrical and mechanical responses of uterine smooth muscle during anaphylaxis in vitro

1958 ◽  
Vol 196 (1) ◽  
pp. 39-43 ◽  
Author(s):  
Seymour Katsh ◽  
Jean M. Marshall
Keyword(s):  
Smooth Muscle ◽  
Membrane Potential ◽  
Action Potential ◽  
Action Potentials ◽  
Specific Antigen ◽  
Resting Membrane Potential ◽  
Uterine Smooth Muscle ◽  
Mechanical Responses ◽  
Spontaneous Contractions

Female guinea pigs were injected with antigen (homologous sperm or ovalbumin) and 14–28 days later ileal segments and both uterine horns were removed. The ileal segments and one of the uterine horns from each animal were tested for responses to drugs, as well as to nonspecific and specific antigen; responses were recorded by means of a kymograph and muscle lever. The contralateral cornua were tested with nonspecific and with specific antigen as well as with drugs; responses were detected and recorded with intracellular electrodes and a mechanotransducer. The notable findings relative to the electronic studies were: within 1–2 minutes following exposure of the sensitized uterus to specific antigen there occurred a) a diminution in resting membrane potential; b) a sudden burst of action potential spikes; c) a contraction of the musculature which was of greater amplitude and of longer duration than those of the spontaneous contractions; d) during the sustained contracture phase, the rate of discharge of action potential spikes was higher than that accompanying spontaneous contractions. After desensitization, specific antigen was without effect. No effect of nonspecific antigen was observed in any of the preparations. After stimulating with specific antigen or with drugs, additional action potentials arose before repolarization from the previous action potential was completed.

Membrane properties and electrogenesis in the distal axons of small dorsal root ganglion neurons in vitro

2012 ◽  
Vol 108 (3) ◽  
pp. 729-740 ◽  
Author(s):  
Dmytro V. Vasylyev ◽  
Stephen G. Waxman
Keyword(s):  
Action Potential ◽  
Action Potentials ◽  
Dorsal Root ◽  
Small Diameter ◽  
Dorsal Root Ganglion Neurons ◽  
Membrane Properties ◽  
Resting Potential ◽  
Drg Neurons ◽  
Ganglion Neurons

Although it is generally thought that sensory transduction occurs at or close to peripheral nerve endings, with action potentials subsequently propagating along the axons of dorsal root ganglia (DRG) neurons toward the central nervous system, the small diameter of nociceptive axons and their endings have made it difficult to estimate their membrane properties and electrogenic characteristics. Even the resting potentials of nociceptive axons are unknown. In this study, we developed the capability to record directly with patch-clamp electrodes from the small-diameter distal axons of DRG neurons in vitro. We showed using current-clamp recordings that 1) these sensory axons have a resting potential of −60.2 ± 1 mV; 2) both tetrodotoxin (TTX)-sensitive (TTX-S) and TTX-resistant (TTX-R) Na+ channels are present and available for activation at resting potential, at densities that can support action potential electrogenesis in these axons; 3) TTX-sensitive channels contribute to the amplification of small depolarizations that are subthreshold with respect to the action potential in these axons; 4) TTX-R channels can support the production of action potentials in these axons; and 5) these TTX-R channels can produce repetitive firing, even at depolarized membrane potentials where TTX-S channels are inactivated. Finally, using voltage-clamp recordings with an action potential as the command, we confirmed the presence of both TTX-S and TTX-R channels, which are activated sequentially during action potential in these axons. These results provide direct evidence for the presence of TTX-S and TTX-R Na+ channels that are functionally available at resting potential and contribute to electrogenesis in small-diameter afferent axons.

Zinc enhances GABAergic transmission in rat neocortical neurons

1993 ◽  
Vol 70 (3) ◽  
pp. 1264-1269 ◽  
Author(s):  
F. M. Zhou ◽  
J. J. Hablitz
Keyword(s):  
Action Potentials ◽  
Excitatory Amino Acid ◽  
Input Resistance ◽  
Synaptic Activity ◽  
Membrane Properties ◽  
Repetitive Firing ◽  
Resting Membrane Potential ◽  
Gamma Aminobutyric Acid ◽  
Postsynaptic Potentials

1. Intracellular recordings were made in layer II-III neurons of rat neocortical slices maintained in vitro. The effect of bath application of zinc (50-300 microM) on evoked synaptic activity and passive membrane properties was examined. 2. Excitatory postsynaptic potentials (EPSPs) mediated by N-methyl-D-aspartate (NMDA) and non-NMDA receptors were recorded in response to electrical stimulation. Zinc did not affect either type of EPSP. Resting membrane potential, repetitive firing properties, and input resistance were not altered by zinc. 3. Inhibitory postsynaptic potentials (IPSPs) were enhanced after zinc application. Zinc also induced generation of large amplitude spontaneous gamma-aminobutyric acid-A (GABAA)- and GABAB-mediated IPSPs. Postsynaptic responses to iontophoretically applied GABA were unaffected. In the presence of zinc, GABAergic synaptic potentials could result in generation of action potentials. 4. Directly evoked IPSPs recorded in the presence of the excitatory amino acid receptor blockers 6-cyano-7-nitroquinoxaline-2,3-dione and 2-amino-5-phosphonovaleric acid were enhanced by zinc. Under these conditions spontaneous IPSPs with superimposed action potentials were present. Baclofen, in the presence of zinc, reduced the amplitude of evoked IPSPs. 5. These results indicate that zinc may be an endogenously occurring neuromodulator. Zinc appears to enhance GABAergic IPSPs by increasing the excitability of inhibitory interneurons, thus resulting in increased GABA release.

scholarly journals Alterations of action potentials and the localization of Nav1.6 sodium channels in spared axons after hemisection injury of the spinal cord in adult rats

2011 ◽  
Vol 105 (3) ◽  
pp. 1033-1044 ◽  
Author(s):  
Arsen S. Hunanyan ◽  
Valentina Alessi ◽  
Samik Patel ◽  
Damien D. Pearse ◽  
Gary Matthews ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Sodium Channels ◽  
Action Potentials ◽  
Molecular Mechanisms ◽  
Input Resistance ◽  
Ultrastructural Changes ◽  
Resting Membrane Potential ◽  
Adult Rats ◽  
Cord Injury

Previously, we reported a pronounced reduction in transmission through surviving axons contralateral to chronic hemisection (HX) of adult rat spinal cord. To examine the cellular and molecular mechanisms responsible for this diminished transmission, we recorded intracellularly from lumbar lateral white matter axons in deeply anesthetized adult rats in vivo and measured the propagation of action potentials (APs) through rubrospinal/reticulospinal tract (RST/RtST) axons contralateral to chronic HX at T10. We found decreased excitability in these axons, manifested by an increased rheobase to trigger APs and longer latency for AP propagation passing the injury level, without significant differences in axonal resting membrane potential and input resistance. These electrophysiological changes were associated with altered spatial localization of Nav1.6 sodium channels along axons: a subset of axons contralateral to the injury exhibited a diffuse localization (>10 μm spread) of Nav1.6 channels, a pattern characteristic of demyelinated axons (Craner MJ, Newcombe J, Black JA, Hartle C, Cuzner ML, Waxman SG. Proc Natl Acad Sci USA 101: 8168–8173, 2004b). This result was substantiated by ultrastructural changes seen with electron microscopy, in which an increased number of large-caliber, demyelinated RST axons were found contralateral to the chronic HX. Therefore, an increased rheobase, pathological changes in the distribution of Nav1.6 sodium channels, and the demyelination of contralateral RST axons are likely responsible for their decreased conduction chronically after HX and thus may provide novel targets for strategies to improve function following incomplete spinal cord injury.

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