Small voltage changes at nerve terminals travel up axons to affect action potential initiation.
Ontology highlight
ABSTRACT:
SUBMITTER: Paradiso K
PROVIDER: S-EPMC3086371 | biostudies-literature | 2009 May
REPOSITORIES: biostudies-literature
Publications
Small voltage changes at nerve terminals travel up axons to affect action potential initiation.
Paradiso Kenneth K Wu Ling-Gang LG
Nature neuroscience 20090406 5
Nerve terminals are generally considered to be the destination points for electrical signals, which propagate unidirectionally from the soma to nerve terminals. We found that small hyperpolarizations or depolarizations ( approximately 10 mV) generated under physiological conditions in rat nerve terminals backpropagated up the axon ( approximately 400-800 microm) and changed the threshold for initiating action potentials and thus firing patterns. These results suggest a mechanism for information ...[more]
Similar Datasets
Project description:Upon the arrival of action potentials at nerve terminals, neurotransmitters are released from synaptic vesicles (SVs) by exocytosis. Ca V 2.1, 2.2, and 2.3 are the major subunits of the voltage-gated calcium channel (VGCC) responsible for increasing intraterminal calcium levels and triggering SV exocytosis in the central nervous system (CNS) synapses. The two-dimensional analysis of Ca V 2 distributions using sodium dodecyl sulfate (SDS)-digested freeze-fracture replica labeling (SDS-FRL) has revealed their numbers, densities, and nanoscale clustering patterns in individual presynaptic active zones. The variation in these properties affects the coupling of VGCCs with calcium sensors on SVs, synaptic efficacy, and temporal precision of transmission. In this study, we summarize how the morphological parameters of Ca V 2 distribution obtained using SDS-FRL differ depending on the different types of synapses and could correspond to functional properties in synaptic transmission.
| S-EPMC8907123 | biostudies-literature
Project description:The steep dependence of exocytosis on Ca(2+) entry at nerve terminals implies that voltage control of both Ca(2+) channel opening and the driving force for Ca(2+) entry are powerful levers in sculpting synaptic efficacy. Using fast, genetically encoded voltage indicators in dissociated primary neurons, we show that at small nerve terminals K(+) channels constrain the peak voltage of the presynaptic action potential (APSYN) to values much lower than those at cell somas. This key APSYN property additionally shows adaptive plasticity: manipulations that increase presynaptic Ca(2+) channel abundance and release probability result in a commensurate lowering of the APSYN peak and narrowing of the waveform, while manipulations that decrease presynaptic Ca(2+) channel abundance do the opposite. This modulation is eliminated upon blockade of Kv3.1 and Kv1 channels. Our studies thus reveal that adaptive plasticity in the APSYN waveform serves as an important regulator of synaptic function.
| S-EPMC4283217 | biostudies-literature
Project description:We investigated voltage-gated sodium channel (NaV1) subunits that regulate action potential initiation in the nerve terminals of vagal nodose C-fibers innervating the esophagus. Extracellular single fiber recordings were made from the nodose C-fibers, with mechanically sensitive nerve terminals in the isolated innervated guinea pig esophagus. NaV1 inhibitors were selectively delivered to the tissue-containing nerve terminals. Graded esophageal distention was used for mechanical stimulation. The NaV1.7 inhibitor PF-05089771 nearly abolished action potential initiation in response to low levels of esophageal distention but only partially inhibited the response to higher levels of esophageal distention. The PF-05089771-insensitive component of the response progressively increased (up to ≈50%) with increasing esophageal distention and was abolished by tetrodotoxin (TTX). In addition to NaV1.7, nodose C-fiber [transient receptor potential channel-vanilloid subfamily member 1 (TRPV1)-positive] neurons retrogradely labeled from the esophagus expressed mRNA for multiple TTX-sensitive NaV1s. The group NaV1.1, NaV1.2, and NaV1.3 inhibitor ICA-121431 inhibited but did not abolish the PF-05089771-insensitive component of the response to high level of esophageal distention. However, combination of ICA-121431 with compound 801, which also inhibits NaV1.7 and NaV1.6, nearly abolished the response to the high level of esophageal distention. Our data indicate that the action potential initiation in esophageal nodose C-fibers evoked by low (innocuous) levels of esophageal distention is mediated by NaV1.7. However, the response evoked by higher (noxious) levels of esophageal distention has a progressively increasing NaV1.7-independent component that involves multiple TTX-sensitive NaV1s. The stimulus intensity-dependent recruitment of NaV1s may offer novel opportunities for strategic targeting of NaV1 subunits for inhibition of nociceptive signaling in visceral C-fibers.NEW & NOTEWORTHY We report that pharmacologically distinguishable voltage-gated sodium channels (NaV1) mediate action potential initiation at low (innocuous) versus high (noxious) intensity of esophageal distention in nerve terminals of vagal nodose C-fibers. Action potential initiation at low intensity is entirely dependent on NaV1.7; however, additional tetrodotoxin (TTX)-sensitive NaV1s are recruited at higher intensity of distention. This is the first demonstration that NaV1s underlying action potential initiation in visceral C-fibers depend on the intensity of the stimulus.
| S-EPMC7654645 | biostudies-literature
Project description:Ca(2+)-activated voltage-dependent K(+) channels (Slo1, KCa1.1, Maxi-K, or BK channel) play a crucial role in controlling neuronal signaling by coupling channel activity to both membrane depolarization and intracellular Ca(2+) signaling. In mammalian brain, immunolabeling experiments have shown staining for Slo1 channels predominantly localized to axons and presynaptic terminals of neurons. We have developed anti-Slo1 mouse monoclonal antibodies that have been extensively characterized for specificity of staining against recombinant Slo1 in heterologous cells, and native Slo1 in mammalian brain, and definitively by the lack of detectable immunoreactivity against brain samples from Slo1 knockout mice. Here we provide precise immunolocalization of Slo1 in rat brain with one of these monoclonal antibodies and show that Slo1 is accumulated in axons and synaptic terminal zones associated with glutamatergic synapses in hippocampus and GABAergic synapses in cerebellum. By using cultured hippocampal pyramidal neurons as a model system, we show that heterologously expressed Slo1 is initially targeted to the axonal surface membrane, and with further development in culture, become localized in presynaptic terminals. These studies provide new insights into the polarized localization of Slo1 channels in mammalian central neurons and provide further evidence for a key role in regulating neurotransmitter release in glutamatergic and GABAergic terminals.
| S-EPMC2605666 | biostudies-literature
Project description:Action Schools! BC (AS! BC) was scaled-up from an efficacy trial to province-wide delivery across 11 years (2004-2015). In this study we: (1) describe strategies that supported implementation and scale-up; (2) evaluate implementation (teachers' physical activity (PA) delivery) and student's PA and cardiorespiratory fitness (CRF) within a cluster randomized controlled trial during years 2 and 3 of scale-up; and (3) assess relationships between teacher-level implementation and student-level outcomes. We classified implementation strategies as process, capacity-building or scale-up strategies. Elementary schools (n = 30) were randomized to intervention (INT; 16 schools; 747 students) or usual practice (UP; 14 schools; 782 students). We measured teachers' PA delivery (n = 179) using weekly logs; students' PA by questionnaire (n = 30 schools) and accelerometry (n = 9 schools); and students' CRF by 20-m shuttle run (n = 25 schools). INT teachers delivered more PA than UP teachers in year 1 (+33.8 min/week, 95% CI 12.7, 54.9) but not year 2 (+18.8 min/week, 95% CI -0.8, 38.3). Unadjusted change in CRF was 36% and 27% higher in INT girls and boys, respectively, compared with their UP peers (year 1; effect size 0.28-0.48). Total PA delivered was associated with change in children's self-reported MVPA (year 1; r = 0.17, p = 0.02). Despite the 'voltage drop', scaling-up school-based PA models is feasible and may enhance children's health. Stakeholders must conceive of new ways to effectively sustain scaled-up health promoting interventions if we are to improve the health of students at a population level. Clinical Trials registration: NCT01412203.
| S-EPMC8153156 | biostudies-literature
Project description:The complex and malleable conduction properties of axons determine how action potentials propagate through extensive axonal arbors to reach synaptic terminals. The excitability of axonal membranes plays a major role in neural circuit function, but because most axons are too thin for conventional electrical recording, their properties remain largely unexplored. To overcome this obstacle, we used a genetically encoded hybrid voltage sensor (hVOS) harboring an axonal targeting motif. Expressing this probe in transgenic mice enabled us to monitor voltage changes optically in two populations of axons in hippocampal slices, the large axons of dentate granule cells (mossy fibers) in the stratum lucidum of the CA3 region and the much finer axons of hilar mossy cells in the inner molecular layer of the dentate gyrus. Action potentials propagated with distinct velocities in each type of axon. Repetitive firing broadened action potentials in both populations, but at an intermediate frequency the degree of broadening differed. Repetitive firing also attenuated action potential amplitudes in both mossy cell and granule cell axons. These results indicate that the features of use-dependent action potential broadening, and possible failure, observed previously in large nerve terminals also appear in much finer unmyelinated axons. Subtle differences in the frequency dependences could influence the propagation of activity through different pathways to excite different populations of neurons. The axonally targeted hVOS probe used here opens up the diverse repertoire of neuronal processes to detailed biophysical study.
| S-EPMC5526655 | biostudies-other
Project description:Botulinum neurotoxins (BoNTs) are highly potent toxins that cleave neuronal SNARE proteins required for neurotransmission, causing flaccid paralysis and death by asphyxiation. Currently, there are no clinical treatments to delay or reverse BoNT-induced blockade of neuromuscular transmission. While aminopyridines have demonstrated varying efficacy in transiently reducing paralysis following BoNT poisoning, the precise mechanisms by which aminopyridines symptomatically treat botulism are not understood. Here we found that activity-dependent potentiation of presynaptic voltage-gated calcium channels (VGCCs) underlies 3,4-diaminopyridine (3,4-DAP)-mediated rescue of neurotransmission in central nervous system synapses and mouse diaphragm neuromuscular junctions fully intoxicated by BoNT serotype A. Combinatorial treatments with 3,4-DAP and VGCC agonists proved synergistic in restoring suprathreshold endplate potentials in mouse diaphragms fully intoxicated by BoNT/A. In contrast, synapses fully intoxicated by BoNT serotypes D or E were refractory to synaptic rescue by any treatment. We interpret these data to propose that increasing the duration or extent of VGCC activation prolongs the opportunity for low-efficiency fusion by fusogenic complexes incorporating BoNT/A-cleaved SNAP-25. The identification of VGCC agonists that rescue neurotransmission in BoNT/A-intoxicated synapses provides compelling evidence for potential therapeutic utility in some cases of human botulism.
| S-EPMC5696531 | biostudies-literature
Project description:Reduction in glutamate release is a key mechanism for neuroprotection and we investigated the effect of isoliquiritigenin (ISL), an active ingredient of Glycyrrhiza with neuroprotective activities, on glutamate release in rat cerebrocortical nerve terminals (synaptosomes). ISL produced a concentration-dependent inhibition of glutamate release and reduced the intraterminal [Ca2+] increase. The inhibition of glutamate release by ISL was prevented after removing extracellular Ca2+ or blocking P/Q-type Ca2+ channels. This inhibition was mediated through the γ-aminobutyric acid type B (GABAB) receptors because ISL was unable to inhibit glutamate release in the presence of baclofen (an GABAB agonist) or CGP3548 (an GABAB antagonist) and docking data revealed that ISL interacted with GABAB receptors. Furthermore, the ISL inhibition of glutamate release was abolished through the inhibition of Gi/o-mediated responses or Gβγ subunits, but not by 8-bromoadenosine 3',5'-cyclic monophosphate or adenylate cyclase inhibition. The ISL inhibition of glutamate release was also abolished through the inhibition of protein kinase C (PKC), and ISL decreased the phosphorylation of PKC. Thus, we inferred that ISL, through GABAB receptor activation and Gβγ-coupled inhibition of P/Q-type Ca2+ channels, suppressed the PKC phosphorylation to cause a decrease in evoked glutamate release at rat cerebrocortical nerve terminals.
| S-EPMC8534184 | biostudies-literature
Project description:With increasing age cognitive performance slows down. This includes cognitive processes essential for motor performance. Additionally, performance of motor tasks becomes less accurate. The objective of the present study was to identify general neural correlates underlying age-related behavioral slowing and the reduction in motor task accuracy. To this end, we continuously recorded EEG activity from 18 younger and 24 older right-handed healthy participants while they were performing a simple finger tapping task. We analyzed the EEG records with respect to local changes in amplitude (power spectrum) as well as phase locking between the two age groups. We found differences between younger and older subjects in the amplitude of post-movement synchronization in the ? band of the sensory-motor and medial prefrontal cortex (mPFC). This post-movement ? amplitude was significantly reduced in older subjects. Moreover, it positively correlated with the accuracy with which subjects performed the motor task at the electrode FCz, which detects activity of the mPFC and the supplementary motor area. In contrast, we found no correlation between the accurate timing of local neural activity, i.e. phase locking in the ?-? frequency band, with the reaction and movement time or the accuracy with which the motor task was performed. Our results show that only post-movement ? amplitude and not ?-? phase locking is involved in the control of movement accuracy. The decreased post-movement ? amplitude in the mPFC of older subjects hints at an impaired deactivation of this area, which may affect the cognitive control of stimulus-induced motor tasks and thereby motor output.
| S-EPMC5703531 | biostudies-literature
Project description:The antidysrhythmic bretylium is useful experimentally because it selectively abolishes neurotransmitter release from sympathetic peripheral nerve terminals. Its mechanism of action seemed settled, but recent results from optical monitoring of single terminals now suggests a new interpretation.Orthograde transport of a dextran-conjugated Ca(2+) indicator to monitor Ca(2+) in nerve terminals of mouse isolated vas deferens with a confocal microscope. In some experiments, local neurotransmitter release was detected by monitoring neuroeffector Ca(2+) transients (NCTs) in adjacent smooth muscles, a local measure of purinergic transmission. Sympathetic terminals were identified with catecholamine fluorescence (UV excitation) or post-experiment immunohistochemistry.Bretylium (10 microM) abolished NCTs at 60/61 junctions over the course of 2 h, indicating effective abolition of neurotransmitter release. However, bretylium did not abolish the field stimulus-induced Ca(2+) transient in most nerve terminals, but did increase both action potential delay (by 2+/-0.4 ms) and absolute refractory period (by 4+/-2 ms). Immunohistochemistry demonstrated that 85-96% of terminals orthogradely filled with a dextran-conjugated fluorescent probe contained Neuropeptide Y (NPY). A formaldehyde-glutaraldehyde-induced catecholamine fluorescence (FAGLU) technique was modified to allow sympathetic terminals to be identified with a Ca(2+) indicator present. Most terminals contained catecholamines (based on FAGLU) or secrete ATP (as NCTs in adjacent smooth muscle cells are abolished).Bretylium can inhibit neurotransmitter release downstream of Ca(2+) influx without abolishing the nerve terminal action potential. Bretylium-induced increases in the absolute refractory period permit living sympathetic terminals to be identified.
| S-EPMC2259200 | biostudies-other