Effects of exercise training on α-motoneurons

2006 ◽  
Vol 101 (4) ◽  
pp. 1228-1236 ◽  
Author(s):  
P. Gardiner ◽  
Y. Dai ◽  
C. J. Heckman
Keyword(s):  
Exercise Training ◽  
Action Potential ◽  
Ion Channel ◽  
Opposite Direction ◽  
Acute Exercise ◽  
Compartment Model ◽  
Resting Membrane Potential ◽  
Voluntary Activity ◽  
Electrophysiological Properties ◽  
Ion Conductances

Evidence is presented that one locus of adaptation in the “neural adaptations to training” is at the level of the α-motoneurons. With increased voluntary activity, these neurons show evidence of dendrite restructuring, increased protein synthesis, increased axon transport of proteins, enhanced neuromuscular transmission dynamics, and changes in electrophysiological properties. The latter include hyperpolarization of the resting membrane potential and voltage threshold, increased rate of action potential development, and increased amplitude of the afterhyperpolarization following the action potential. Many of these changes demonstrate intensity-related adaptations and are in the opposite direction under conditions in which chronic activity is reduced. A five-compartment model of rat motoneurons that innervate fast and slow muscle fibers (termed “fast” and “slow” motoneurons in this paper), including 10 active ion conductances, was used to attempt to reproduce exercise training-induced adaptations in electrophysiological properties. The results suggest that adaptations in α-motoneurons with exercise training may involve alterations in ion conductances, which may, in turn, include changes in the gene expression of the ion channel subunits, which underlie these conductances. Interestingly, the acute neuromodulatory effects of monoamines on motoneuron properties, which would be a factor during acute exercise as these monoaminergic systems are activated, appear to be in the opposite direction to changes measured in endurance-trained motoneurons that are at rest. It may be that regular increases in motoneuronal excitability during exercise via these monoaminergic systems in fact render the motoneurons less excitable when at rest. More research is required to establish the relationships between exercise training, resting and exercise motoneuron excitability, ion channel modulation, and the effects of neuromodulators.

scholarly journals Melatonin Reduces Excitability in Dorsal Root Ganglia Neurons with Inflection on the Repolarization Phase of the Action Potential

2019 ◽  
Vol 20 (11) ◽  
pp. 2611 ◽  
Author(s):  
Klausen Oliveira-Abreu ◽  
Nathalia Silva-dos-Santos ◽  
Andrelina Coelho-de-Souza ◽  
Francisco Ferreira-da-Silva ◽  
Kerly Silva-Alves ◽  
...  
Keyword(s):  
Action Potential ◽  
Dorsal Root Ganglia ◽  
Dorsal Root ◽  
Neuronal Excitability ◽  
Input Resistance ◽  
Cell Types ◽  
Neuronal Population ◽  
Resting Membrane Potential ◽  
Electrophysiological Properties ◽  
Repolarization Phase

Melatonin is a neurohormone produced and secreted at night by pineal gland. Many effects of melatonin have already been described, for example: Activation of potassium channels in the suprachiasmatic nucleus and inhibition of excitability of a sub-population of neurons of the dorsal root ganglia (DRG). The DRG is described as a structure with several neuronal populations. One classification, based on the repolarizing phase of the action potential (AP), divides DRG neurons into two types: Without (N0) and with (Ninf) inflection on the repolarization phase of the action potential. We have previously demonstrated that melatonin inhibits excitability in N0 neurons, and in the present work, we aimed to investigate the melatonin effects on the other neurons (Ninf) of the DRG neuronal population. This investigation was done using sharp microelectrode technique in the current clamp mode. Melatonin (0.01–1000.0 nM) showed inhibitory activity on neuronal excitability, which can be observed by the blockade of the AP and by the increase in rheobase. However, we observed that, while some neurons were sensitive to melatonin effect on excitability (excitability melatonin sensitive—EMS), other neurons were not sensitive to melatonin effect on excitability (excitability melatonin not sensitive—EMNS). Concerning the passive electrophysiological properties of the neurons, melatonin caused a hyperpolarization of the resting membrane potential in both cell types. Regarding the input resistance (Rin), melatonin did not change this parameter in the EMS cells, but increased its values in the EMNS cells. Melatonin also altered several AP parameters in EMS cells, the most conspicuously changed was the (dV/dt)max of AP depolarization, which is in coherence with melatonin effects on excitability. Otherwise, in EMNS cells, melatonin (0.1–1000.0 nM) induced no alteration of (dV/dt)max of AP depolarization. Thus, taking these data together, and the data of previous publication on melatonin effect on N0 neurons shows that this substance has a greater pharmacological potency on Ninf neurons. We suggest that melatonin has important physiological function related to Ninf neurons and this is likely to bear a potential relevant therapeutic use, since Ninf neurons are related to nociception.

Sciatic Chronic Constriction Injury Produces Cell-Type-Specific Changes in the Electrophysiological Properties of Rat Substantia Gelatinosa Neurons

2006 ◽  
Vol 96 (2) ◽  
pp. 579-590 ◽  
Author(s):  
Sridhar Balasubramanyan ◽  
Patrick L. Stemkowski ◽  
Martin J. Stebbing ◽  
Peter A. Smith
Keyword(s):  
Action Potential ◽  
Dorsal Horn ◽  
Chronic Constriction Injury ◽  
Input Resistance ◽  
Substantia Gelatinosa ◽  
Resting Membrane Potential ◽  
Cellular Mechanisms ◽  
Electrophysiological Properties ◽  
Putative Role ◽  
Cell Recording

Peripheral nerve injury increases spontaneous action potential discharge in spinal dorsal horn neurons and augments their response to peripheral stimulation. This “central hypersensitivity, ” which relates to the onset and persistence of neuropathic pain, reflects spontaneous activity in primary afferent fibers as well as long-term changes in the intrinsic properties of the dorsal horn (centralization). To isolate and investigate cellular mechanisms underlying “centralization,” sciatic nerves of 20-day-old rats were subjected to 13–25 days of chronic constriction injury (CCI; Mosconi-Kruger polyethylene cuff model). Spinal cord slices were then acutely prepared from sham-operated or CCI animals, and whole cell recording was used to compare the properties of five types of substantia gelatinosa neuron. These were defined as tonic, irregular, phasic, transient, or delay according to their discharge pattern in response to depolarizing current. CCI did not affect resting membrane potential, rheobase, or input resistance in any neuron type but increased the amplitude and frequency of spontaneous and miniature excitatory postsynaptic currents (EPSCs) in delay, transient, and irregular cells. These changes involved alterations in the action potential-independent neurotransmitter release machinery and possible increases in the postsynaptic effectiveness of glutamate. By contrast, in tonic cells, CCI reduced the amplitude and frequency of spontaneous and miniature EPSCs. Such changes may relate to the putative role of tonic cells as inhibitory GABAergic interneurons, whereas increased synaptic drive to delay cells may relate to their putative role as the excitatory output neurons of the substantia gelatinosa. Complementary changes in synaptic excitation of inhibitory and excitatory neurons may thus contribute to pain centralization.

Changes in the electrophysiological properties of cat spinal motoneurons following the intramuscular injection of adriamycin compared with changes in the properties of motoneurons in aged cats

1995 ◽  
Vol 74 (5) ◽  
pp. 1972-1981 ◽  
Author(s):  
R. H. Liu ◽  
J. Yamuy ◽  
M. C. Xi ◽  
F. R. Morales ◽  
M. H. Chase
Keyword(s):  
Electrical Properties ◽  
Action Potential ◽  
Conduction Velocity ◽  
Time Constant ◽  
Correlation Coefficients ◽  
Input Resistance ◽  
Resting Membrane Potential ◽  
Electrophysiological Properties ◽  
Axonal Conduction ◽  
Adult Cat

1. This study was undertaken to investigate the effects of adriamycin (ADM, Doxorubicin) on the basic electrophysiological properties of spinal cord motoneurons in the adult cat. ADM was injected into the biceps, gastrocnemius, semitendinosus, and semimembranosus muscles of the left hindlimb (1.2 mg per muscle). Intracellular recordings from motoneurons innervating these muscles were carried out 12, 20, or 40 days after ADM administration and from corresponding motoneurons in untreated control cats. 2. Twelve days after ADM injection, motoneurons innervating ADM-treated muscles (ADM MNs) exhibited statistically significant increases in input resistance, membrane time constant, and amplitude of the action potential's afterhyperpolarization (AHP). In addition, there was a statistically significant decrease in rheobase and in the delay between the action potential of the initial segment (IS) and that of the somadendritic (SD) portion of the motoneuron (IS-SD delay). There were no significant changes in the resting membrane potential, threshold depolarization, action potential amplitude, or axonal conduction velocity. 3. The changes in electrical properties of motoneurons at 20 and 40 days after ADM injection were qualitatively similar to those observed at 12 days. However, at 40 days after ADM injection there was a statistically significant decrease in the axonal conduction velocity of the ADM MNs. 4. The normal correlations that are present between the AHP duration and electrical properties of the control motoneurons were observed in the ADM MNs, e.g., AHP duration was positively correlated with the input resistance and time constant and negatively correlated with the axonal conduction velocity. The correlation coefficients, however, were reduced in comparison with the control data. 5. This study demonstrates that ADM exerts significant effects on the electrical properties of motoneurons when injected into their target muscles. The majority of the changes in motoneuron electrical properties caused by ADM resemble those observed in motoneurons of aged cats. Additional research is required to determine whether the specific changes induced in motoneurons by ADM and those that occur in motoneurons in old age are due to similar degradative mechanisms.

scholarly journals MicroRNA Biophysically Modulates Cardiac Action Potential by Direct Binding to Ion Channel

Circulation ◽  
2021 ◽  
Vol 143 (16) ◽  
pp. 1597-1613 ◽  
Author(s):  
Dandan Yang ◽  
Xiaoping Wan ◽  
Adrienne T. Dennis ◽  
Emre Bektik ◽  
Zhihua Wang ◽  
...  
Keyword(s):  
Membrane Potential ◽  
Rna Interference ◽  
Action Potential ◽  
Ion Channel ◽  
Cardiac Electrophysiology ◽  
Ex Vivo ◽  
Proximity Ligation Assay ◽  
Resting Membrane Potential ◽  
Seed Region ◽  
Single Nucleotide

Background: MicroRNAs (miRs) play critical roles in regulation of numerous biological events, including cardiac electrophysiology and arrhythmia, through a canonical RNA interference mechanism. It remains unknown whether endogenous miRs modulate physiologic homeostasis of the heart through noncanonical mechanisms. Methods: We focused on the predominant miR of the heart (miR1) and investigated whether miR1 could physically bind with ion channels in cardiomyocytes by electrophoretic mobility shift assay, in situ proximity ligation assay, RNA pull down, and RNA immunoprecipitation assays. The functional modulations of cellular electrophysiology were evaluated by inside-out and whole-cell patch clamp. Mutagenesis of miR1 and the ion channel was used to understand the underlying mechanism. The effect on the heart ex vivo was demonstrated through investigating arrhythmia-associated human single nucleotide polymorphisms with miR1-deficient mice. Results: We found that endogenous miR1 could physically bind with cardiac membrane proteins, including an inward-rectifier potassium channel Kir2.1. The miR1–Kir2.1 physical interaction was observed in mouse, guinea pig, canine, and human cardiomyocytes. miR1 quickly and significantly suppressed I K1 at sub–pmol/L concentration, which is close to endogenous miR expression level. Acute presence of miR1 depolarized resting membrane potential and prolonged final repolarization of the action potential in cardiomyocytes. We identified 3 miR1-binding residues on the C-terminus of Kir2.1. Mechanistically, miR1 binds to the pore-facing G-loop of Kir2.1 through the core sequence AAGAAG, which is outside its RNA interference seed region. This biophysical modulation is involved in the dysregulation of gain-of-function Kir2.1–M301K mutation in short QT or atrial fibrillation. We found that an arrhythmia-associated human single nucleotide polymorphism of miR1 (hSNP14A/G) specifically disrupts the biophysical modulation while retaining the RNA interference function. It is remarkable that miR1 but not hSNP14A/G relieved the hyperpolarized resting membrane potential in miR1-deficient cardiomyocytes, improved the conduction velocity, and eliminated the high inducibility of arrhythmia in miR1-deficient hearts ex vivo. Conclusions: Our study reveals a novel evolutionarily conserved biophysical action of endogenous miRs in modulating cardiac electrophysiology. Our discovery of miRs’ biophysical modulation provides a more comprehensive understanding of ion channel dysregulation and may provide new insights into the pathogenesis of cardiac arrhythmias.

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.

Temperature dependence of electrophysiological properties of guinea pig and ground squirrel myocytes

1992 ◽  
Vol 263 (1) ◽  
pp. R177-R184 ◽  
Author(s):  
J. C. Herve ◽  
K. Yamaoka ◽  
V. W. Twist ◽  
T. Powell ◽  
J. C. Ellory ◽  
...  
Keyword(s):  
Membrane Potential ◽  
Guinea Pig ◽  
Action Potential ◽  
Ground Squirrel ◽  
Calcium Release ◽  
Maximum Amplitude ◽  
Calcium Currents ◽  
Resting Membrane Potential ◽  
Electrophysiological Properties ◽  
Time To Peak

The effects of changing temperature on the electrophysiology of isolated cardiac myocytes of the guinea pig and Richardson's ground squirrel were studied by patch-clamp techniques. In cells from both species, the resting membrane potential declined on cooling from 36 to 12 degrees C by approximately 6 mV. The duration of the plateau of the action potential in guinea pig cells increased monotonically on cooling. In contrast, the action potential of ground squirrel cells showed a biphasic response, increasing in duration from 36 to 24 degrees C and then decreasing on cooling from 24 to 12 degrees C. From voltage-clamp studies, the properties of L-type calcium currents (ICa) on cooling were compared in the two species and were found to be similar: In both cases, ICa decreased in amplitude from approximately 2 nA peak current at 36 degrees C to less than 400 pA at 12 degrees C. The Q10 of both the maximum amplitude and time to peak for ICa in both species was approximately 1.8. The time for half inactivation had a greater Q10 of 2.5-3. It is concluded that, surprisingly, factors affecting the resting membrane potential and properties of L-type calcium channels are not major contributors to cardiac dysfunction on cooling. Rather, it is sarcoplasmic reticulum calcium release and reuptake that are likely to be the most important cold-sensitive processes.

Carbachol inhibits electrophysiological effects of cyclic AMP in ventricular myocytes

1986 ◽  
Vol 251 (3) ◽  
pp. H601-H611 ◽  
Author(s):  
D. P. Rardon ◽  
A. J. Pappano
Keyword(s):  
Cyclic Amp ◽  
Action Potential ◽  
Ventricular Myocytes ◽  
Fold Increase ◽  
Resting Membrane Potential ◽  
Muscarinic Agonists ◽  
Electrophysiological Properties ◽  
Beta Adrenoceptor ◽  
Mediated Effects ◽  
Electrophysiological Effects

Muscarinic agonists inhibit beta-adrenoceptor-mediated electrophysiological effects in mammalian cardiac ventricular tissues. However, the site or sites of interaction are not entirely clarified. To address this problem, the effect of carbachol on isoproterenol-, 3-isobutyl-1-methylxanthine-, and forskolin-induced action potential changes was examined in guinea pig ventricular myocytes. Following enzymatic dispersion, myocytes had a resting membrane potential of -81.3 +/- 3 mV in 5.4 mM K+ Tyrode solution, and stimulated action potentials were 348 +/- 17 ms in duration (n = 17). Elevated extracellular [K+] ([K+]o) depolarized the membrane 56.5 mV per 10-fold increase in [K+]o. The estimated intracellular K+ activity was 115.7 mM. Carbachol (10(-6) M) alone produced no electrophysiological changes but antagonized isoproterenol-, 3-isobutyl-1-methylxanthine-, and forskolin-induced action potential prolongation by 84 +/- 11, 88 +/- 17, and 83 +/- 14%, respectively. Transient depolarizations produced in isoproterenol (10(-8) M), 3-isobutyl-1-methylxanthine (10(-5) M), and forskolin (10(-7) M), but not those produced in ouabain (10(-6) M), were antagonized by carbachol (10(-6) M). These data show that enzymatically dispersed myocytes maintain pharmacological and electrophysiological properties similar to those of cells in tissues, carbachol antagonizes electrophysiological effects of isoproterenol, 3-isobutyl-1-methylxanthine, and forskolin, and carbachol inhibits cyclic AMP-mediated effects at a site or sites in the cyclic AMP cascade distal to the catalytic unit of adenylate cyclase.

scholarly journals pH-Insensitive FRET Voltage Dyes

2007 ◽  
Vol 12 (5) ◽  
pp. 656-667 ◽  
Author(s):  
Michael P. Maher ◽  
Nyan-Tsz Wu ◽  
Hong Ao
Keyword(s):  
Ion Channel ◽  
High Throughput ◽  
Resonance Energy Transfer ◽  
Resonance Energy ◽  
High Sensitivity ◽  
Fast Response ◽  
Resting Membrane Potential ◽  
Absolute Calibration ◽  
High Throughput Assay ◽  
Voltage Sensitive Dyes

Many high-throughput ion channel assays require the use of voltage-sensitive dyes to detect channel activity in the presence of test compounds. Dye systems employing Förster resonance energy transfer (FRET) between 2 membrane-bound dyes are advantageous in combining high sensitivity, relatively fast response, and ratiometric output. The most widely used FRET voltage dye system employs a coumarin fluorescence donor whose excitation spectrum is pH dependent. The authors have validated a new class of voltage-sensitive FRET donors based on a pyrene moiety. These dyes are significantly brighter than CC2-DMPE and are not pH sensitive in the physiological range. With the new dye system, the authors demonstrate a new high-throughput assay for the acid-sensing ion channel (ASIC) family. They also introduce a novel method for absolute calibration of voltage-sensitive dyes, simultaneously determining the resting membrane potential of a cell. ( Journal of Biomolecular Screening 2007:656-667)

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