scholarly journals Quantitation of single action potential-evoked Ca2+ signals in CA1 pyramidal neuron presynaptic terminals

2018 ◽  
Author(s):  
Emily Church ◽  
Edaeni Hamid ◽  
Simon Alford
Keyword(s):  
Action Potential ◽  
Action Potentials ◽  
Repetitive Stimulation ◽  
Short Term ◽  
C2 Domains ◽  
Single Action ◽  
Decay Times ◽  
Diffusion Rates ◽  
Spatio Temporal ◽  
Ca1 Pyramidal Neuron

AbstractPresynaptic Ca2+ evokes exocytosis, endocytosis, and short-term synaptic plasticity. However, Ca2+ flux and interactions at presynaptic molecular targets are difficult to determine, because imaging has limited resolution. We measured single varicosity presynaptic Ca2+ using Ca2+ dyes as buffers, and constructed models of Ca2+ dispersal. Action potentials evoked Ca2+ transients (peak amplitude, 789±39 nM, within 2 ms of stimulation; decay times, 119±10 ms) with little variation when measured with low-affinity dye. Endogenous Ca2+ buffering capacities, action potential-evoked free [Ca2+]¡ and total amounts entering terminals were determined using high-affinity Ca2+ dyes to buffer Ca2+ transients. These data constrained Monte Carlo (MCell) simulations of Ca2+ entry, buffering, and removal. Data were well-fit with simulations of experimentally-determined Ca2+ fluxes, buffered by simulated Calbindin28K. Simulations were consistent with clustered Ca2+ entry followed within 2 ms by diffusion throughout the varicosity. Repetitive stimulation caused free varicosity Ca2+ to sum. However, simulated in nanometer domains, its removal by pumps and buffering was negligible, while diffusion rates were high. Thus, Ca2+ within tens of nanometers of entry, did not accumulate during sequential stimuli. A model of synaptotagmin1-Ca2+ binding indicates that even with 10 μM free varicosity Ca2+, synaptogmin1 must be within tens of nanometers of channels to ensure occupation of all its Ca2+ binding sites. Repetitive stimulation, which evokes short-term synaptic enhancement, does not modify probabilities of Ca2+ fully occupying synaptotagmin1’s C2 domains, suggesting that enhancement is not mediated by Ca2+-synaptotagmin1. We conclude that at spatio-temporal scale of fusion machines, Ca2+ necessary for their activation is diffusion dominated.

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.

Electrophysiological properties of neurons within the nucleus ambiguus of adult guinea pigs

1991 ◽  
Vol 66 (3) ◽  
pp. 744-761 ◽  
Author(s):  
S. M. Johnson ◽  
P. A. Getting
Keyword(s):  
Action Potential ◽  
Action Potentials ◽  
Outward Current ◽  
Nucleus Ambiguus ◽  
Transient Outward Current ◽  
Maximum Magnitude ◽  
Action Potential Firing ◽  
Onset Of Action ◽  
Electrophysiological Properties ◽  
Single Action

1. The purpose of this study was to determine the electrophysiological properties of neurons within the region of the nucleus ambiguus (NA), an area that contains the ventral respiratory group. By the use of an in vitro brain stem slice preparation, intracellular recordings from neurons in this region (to be referred to as NA neurons, n = 235) revealed the following properties: postinhibitory rebound (PIR), delayed excitation (DE), adaptation, and posttetanic hyperpolarization (PTH). NA neurons were separated into three groups on the basis of their expression of PIR and DE: PIR cells (58%), DE cells (31%), and Non cells (10%). Non cells expressed neither PIR nor DE and no cells expressed both PIR and DE. 2. PIR was a transient depolarization that produced a single action potential or a burst of action potentials when the cell was released from hyperpolarization. In the presence of tetrodotoxin (TTX), the maximum magnitude of PIR was 7-12 mV. Under voltage-clamp conditions, hyperpolarizing voltage steps elicited a small inward current during the hyperpolarization and a small inward tail current on release from hyperpolarization. These currents, which mediate PIR, were most likely due to Q-current because they were blocked with extracellular cesium and were insensitive to barium. 3. DE was a delay in the onset of action potential firing when cells were hyperpolarized before application of depolarizing current. When cells were hyperpolarized to -90 mV for greater than or equal to 300 ms, maximum delays ranged from 150 to 450 ms. The transient outward current underlying DE was presumed to be A-current because of the current's activation and inactivation characteristics and its elimination by 4-aminopyridine (4-AP). 4. Adaptation was examined by applying depolarizing current for 2.0 s and measuring the frequency of evoked action potentials. Although there was a large degree of variability in the degree of adaptation, PIR cells tended to express less adaptation than DE and Non cells. Nearly three-fourths of all NA neurons adapted rapidly (i.e., 50% adaptation in less than 200 ms), but PIR cells tended to adapt faster than DE and Non cells. PTH after a train of action potentials was relatively rare and occurred more often in DE cells (43%) and Non cells (33%) than in PIR cells (13%). PTH had a magnitude of up to 18 mV and time constants that reflected the presence of one (1.7 +/- 1.4 s, mean +/- SD) or two components (0.28 +/- 0.13 and 4.1 +/- 2.2 s).(ABSTRACT TRUNCATED AT 400 WORDS)

Excitable Membrane Properties of Neurons

2020 ◽  
Author(s):  
Leonard K. Kaczmarek
Keyword(s):  
Action Potential ◽  
Action Potentials ◽  
Cell Biology ◽  
Neuronal Firing ◽  
Membrane Properties ◽  
Potassium Ions ◽  
Single Action ◽  
Sodium Calcium ◽  
Different Types ◽  
Order Of Magnitude

The intrinsic electrical properties of neurons are extremely varied. For example, the width of action potentials in different neurons varies by more than an order of magnitude. In response to prolonged stimulation, some neurons generate repeated action potential hundreds of times a second, while others fire only a single action potential or adapt very rapidly. These differences result from the expression of different types of ion channels in the plasma membrane. The dominant channels that shape neuronal firing patterns are those that are selective for sodium, calcium, and potassium ions. This chapter provides a brief overview of the biophysical properties of each of these classes of channel, their role in shaping the electrical personality of a neuron, and how interactions of these channels with cytoplasmic factors shape the overall cell biology of a neuron.

scholarly journals The Effect of Aconitine on the Giant Axon of the Squid

1964 ◽  
Vol 47 (4) ◽  
pp. 719-733 ◽  
Author(s):  
W. H. Herzog ◽  
R. M. Feibel ◽  
S. H. Bryant
Keyword(s):  
Membrane Potential ◽  
Action Potential ◽  
Action Potentials ◽  
Giant Axon ◽  
Membrane Resistance ◽  
Repetitive Stimulation ◽  
Resting Membrane Potential ◽  
Sustained Activity ◽  
Frequency Of Stimulation ◽  
Sodium And Potassium

In the giant axon of Loligo pealii, "aconitine potent" Merck added to the bath (10-7 to 1.25 x 10-6 gm/ml) (a) had no effect on resting membrane potential, membrane resistance and rectification, membrane response to subthreshold currents, critical depolarization, or action potential, but (b) on repetitive stimulation produced oscillations of membrane potential after the spike, depolarization, and decrease of membrane resistance. The effect sums with successive action potentials; it increases with concentration of aconitine, time of exposure, and frequency of stimulation. When the oscillations are large enough and the membrane potential is 51.6 ± SD 1.5 mv a burst of self-sustained activity begins; it usually lasts 20 to 70 sec. and at its end the membrane potential is 41.5 ± SD 1.9 mv. Repolarization occurs with a time constant of 2.5 to 11.1 min. Substitution of choline for external sodium after a burst hyperpolarizes the membrane to -70 mv, and return to normal external sodium depolarizes again beyond the resting membrane potential. The effect of aconitine on the membrane is attributed to an increase of sodium and potassium or chloride conductances following the action potential.

KATP channels depress force by reducing action potential amplitude in mouse EDL and soleus muscle

2003 ◽  
Vol 285 (6) ◽  
pp. C1464-C1474 ◽  
Author(s):  
B. Gong ◽  
D. Legault ◽  
T. Miki ◽  
S. Seino ◽  
J. M. Renaud
Keyword(s):  
Action Potential ◽  
Action Potentials ◽  
Metabolic Stress ◽  
Katp Channels ◽  
Channel Blockers ◽  
Action Potential Amplitude ◽  
Membrane Excitability ◽  
M Wave ◽  
Single Action ◽  
Potential Amplitude

Although ATP-sensitive K+ (KATP) channel openers depress force, channel blockers have no effect. Furthermore, the effects of channel openers on single action potentials are quite small. These facts raise questions as to whether 1) channel openers reduce force via an activation of KATP channels or via some nonspecific effects and 2) the reduction in force by KATP channels operates by changes in amplitude and duration of the action potential. To answer the first question we tested the hypothesis that pinacidil, a channel opener, does not affect force during fatigue in muscles of Kir6.2-/- mice that have no cell membrane KATP channel activity. When wild-type extensor digitorum longus (EDL) and soleus muscles were stimulated to fatigue with one tetanus per second, pinacidil increased the rate at which force decreased, prevented a rise in resting tension, and improved force recovery. Pinacidil had none of these effects in Kir6.2-/- muscles. To answer the second question, we tested the hypothesis that the effects of KATP channels on membrane excitability are greater during action potential trains than on single action potentials, especially during metabolic stress such as fatigue. During fatigue, M wave areas of control soleus remained constant for 90 s, suggesting no change in action potential amplitude for half of the fatigue period. In the presence of pinacidil, the decrease in M wave areas became significant within 30 s, during which time the rate of fatigue also became significantly faster compared with control muscles. It is therefore concluded that, once activated, KATP channels depress force and that this depression involves a reduction in action potential amplitude.

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.

Propagation of action potentials in the dendrites of neurons from rat spinal cord slice cultures

1996 ◽  
Vol 75 (1) ◽  
pp. 154-170 ◽  
Author(s):  
M. E. Larkum ◽  
M. G. Rioult ◽  
H. R. Luscher
Keyword(s):  
Spinal Cord ◽  
Action Potential ◽  
Calcium Imaging ◽  
Action Potentials ◽  
Synaptic Activity ◽  
Rat Spinal Cord ◽  
Voltage Sensitive Dye ◽  
Single Action ◽  
Before And After ◽  
Time Courses

1. We examined the propagation of action potentials in the dendrites of ventrally located presumed motoneurons of organotypic rat spinal cord cultures. Simultaneous patch electrode recordings were made from the dendrites and somata of individual cells. In other experiments we visualized the membrane voltage over all the proximal dendrites simultaneously using a voltage-sensitive dye and an array of photodiodes. Calcium imaging was used to measure the dendritic rise in Ca2+ accompanying the propagating action potentials. 2. Spontaneous and evoked action potentials were recorded using high-resistance patch electrodes with separations of 30-423 microm between the somatic and dendritic electrodes. 3. Action potentials recorded in the dendrites varied considerably in amplitude but were larger than would be expected if the dendrites were to behave as passive cables (sometimes little or no decrement was seen for distances of > 100 microm). Because the amplitude of the action potentials in different dendrites was not a simple function of distance from the soma, we suggest that the conductance responsible for the boosting of the action potential amplitude varied in density from dendrite to dendrite and possibly along each dendrite. 4. The dendritic action potentials were usually smaller and broader and arrived later at the dendritic electrode than at the somatic electrode irrespective of whether stimulation occurred at the dendrite or soma or as a result of spontaneous synaptic activity. This is clear evidence that the action potential is initiated at or near the soma and spreads out into the dendrites. The conduction velocity of the propagating action potential was estimated to be 0.5 m/s. 5. The voltage time courses of previously recorded action potentials were generated at the soma using voltage clamp before and after applying 1 microM tetrodotoxin (TTX) over the soma and dendrites. TTX reduced the amplitude of the action potential at the dendritic electrode to a value in the range expected for dendrites that behave as passive cables. This indicates that the conductance responsible for the actively propagating action potentials is a Na+ conductance. 6. The amplitude of the dendritic action potential could also be initially reduced more than the somatic action potential using 1-10 mM QX-314 (an intracellular sodium channel blocker) in the dendritic electrode as the drug diffused from the dendritic electrode toward the soma. Furthermore, in some cases the action potential elicited by current injection into the dendrite had two components. The first component was blocked by QX-314 in the first few seconds of the diffusion of the blocker. 7. In some cells, an afterdepolarizing potential (ADP) was more prominent in the dendrite than in the soma. This ADP could be reversibly blocked by 1 mM Ni2+ or by perfusion of a nominally Ca2+-free solution over the soma and dendrites. This suggests that the back-propagating action potential caused an influx of Ca2+ predominantly in the dendrites. 8. With the use of a voltage-sensitive dye (di-8-ANEPPS) and an array of photodiodes, the action potential was tracked along all the proximal dendrites simultaneously. The results confirmed that the action potential propagated actively, in contrast to similarly measured hyperpolarizing pulses that spread passively. There were also indications that the action potential was not uniformly propagated in all the dendrites, suggesting the possibility that the distribution of Na+ channels over the dendritic membrane is not uniform. 9. Calcium imaging with the Ca2+ fluorescent indicator Fluo-3 showed a larger percentage change in fluorescence in the dendrites than in the soma. Both bursts and single action potentials elicited sharp rises in fluorescence in the proximal dendrites, suggesting that the back-propagating action potential causes a concomitant rise in intracellular calcium concentration...

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.

scholarly journals Modulation of sarcoplasmic reticulum Ca2+ release in skeletal muscle expressing ryanodine receptor impaired in regulation by calmodulin and S100A1

2011 ◽  
Vol 300 (5) ◽  
pp. C998-C1012 ◽  
Author(s):  
Naohiro Yamaguchi ◽  
Benjamin L. Prosser ◽  
Farshid Ghassemi ◽  
Le Xu ◽  
Daniel A. Pasek ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Sarcoplasmic Reticulum ◽  
Action Potential ◽  
Ryanodine Receptor ◽  
Repetitive Stimulation ◽  
Mutant Mice ◽  
High Frequency Stimulation ◽  
Single Action ◽  
Single Action Potential ◽  
Release Flux

In vitro, calmodulin (CaM) and S100A1 activate the skeletal muscle ryanodine receptor ion channel (RyR1) at submicromolar Ca2+ concentrations, whereas at micromolar Ca2+ concentrations, CaM inhibits RyR1. One amino acid substitution (RyR1-L3625D) has previously been demonstrated to impair CaM binding and regulation of RyR1. Here we show that the RyR1-L3625D substitution also abolishes S100A1 binding. To determine the physiological relevance of these findings, mutant mice were generated with the RyR1-L3625D substitution in exon 74, which encodes the CaM and S100A1 binding domain of RyR1. Homozygous mutant mice ( Ryr1 D/D) were viable and appeared normal. However, single RyR1 channel recordings from Ryr1 D/D mice exhibited impaired activation by CaM and S100A1 and impaired CaCaM inhibition. Isolated flexor digitorum brevis muscle fibers from Ryr1 D/D mice had depressed Ca2+ transients when stimulated by a single action potential. However, during repetitive stimulation, the mutant fibers demonstrated greater relative summation of the Ca2+ transients. Consistently, in vivo stimulation of tibialis anterior muscles in Ryr1 D/D mice demonstrated reduced twitch force in response to a single action potential, but greater summation of force during high-frequency stimulation. During repetitive stimulation, Ryr1 D/D fibers exhibited slowed inactivation of sarcoplasmic reticulum Ca2+ release flux, consistent with increased summation of the Ca2+ transient and contractile force. Peak Ca2+ release flux was suppressed at all voltages in voltage-clamped Ryr1 D/D fibers. The results suggest that the RyR1-L3625D mutation removes both an early activating effect of S100A1 and CaM and delayed suppressing effect of CaCaM on RyR1 Ca2+ release, providing new insights into CaM and S100A1 regulation of skeletal muscle excitation-contraction coupling.

scholarly journals Suppression of sensory to motor synaptic transmission and narrowing of the sensory neurone action potential by arginine vasotocin in Aplysia californica

1987 ◽  
Vol 128 (1) ◽  
pp. 47-62
Author(s):  
J. Goldberg ◽  
W. Colmers ◽  
J. Edstrom ◽  
K. Lukowiak
Keyword(s):  
Action Potential ◽  
Synaptic Transmission ◽  
Action Potentials ◽  
Physiological Role ◽  
Arginine Vasotocin ◽  
Sensory Cells ◽  
Sensory Neurone ◽  
Single Action ◽  
Withdrawal Reflex ◽  
Homosynaptic Depression

The vertebrate neurohypophysial peptide arginine vasotocin (AVT), which may be endogenous to the Aplysia central nervous system, was tested for its effect on sensory to motor neurone synaptic transmission. In the semi-intact preparation, superfusion of AVT (10(−6) moll-1) over the abdominal ganglion decreased the amplitude of both the gill withdrawal reflex and the short-latency excitatory postsynaptic potentials (EPSPs) evoked in gill and siphon motor neurones by single action potentials elicited in sensory neurones. AVT slowed the rate of rise of the EPSP, enhanced the rate of homosynaptic depression, and reversibly decreased the duration of the action potential of mechanosensory neurones in isolated, perfused abdominal and pleural ganglia. Frequency-dependent prolongation of action potentials of pleural sensory cells was also decreased by application of AVT. Because this peptide has been shown to modulate the gill withdrawal reflex and its subsequent habituation, the hypothesis that AVT plays a physiological role in the expression of the suppressed behavioural state is proposed. In addition, it is proposed that modulation of the reflex by AVT occurs in part by shortening the duration of the sensory neurone action potential.

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