Difference between revisions of "Event:682"

From AOP-Wiki
Jump to: navigation, search
(References)
 
(17 intermediate revisions by 2 users not shown)
Line 6: Line 6:
  
 
== Key Event Overview ==
 
== Key Event Overview ==
Please follow link to [//{{SERVERNAME}}/aopportal/events/{{PAGENAMEE}} widget page] to edit this section. <span style="color:#FF0000">'''If you manually enter text in this section, it will get automatically altered or deleted in subsequent edits using the widgets.'''</span>
+
Please follow link to [//{{SERVERNAME}}/events/{{PAGENAMEE}} widget page] to edit this section.
 +
 
 +
<span style="color:#FF0000">'''If you manually enter text in this section, it will get automatically altered or deleted in subsequent edits using the widgets.'''</span>
  
 
=== AOPs Including This Key Event ===
 
=== AOPs Including This Key Event ===
Line 20: Line 22:
 
|-
 
|-
  
|[[Aop:10|Neurotoxicity induced by competitive antagonists of ionotropic GABA receptors]]||KE||[[Aop:10#Essentiality of the Key Events|Strong]]
+
|[[Aop:10|Binding to the picrotoxin site of ionotropic GABA receptors leading to epileptic seizures]]||KE||[[Aop:10#Essentiality of the Key Events|Strong]]
  
 
|-
 
|-
Line 37: Line 39:
 
|-
 
|-
  
| mouse || Mus musculus || [[Event:682#Evidence Supporting Taxonomic Applicability|Strong]] || [http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id=10090 NCBI]
+
|mouse||Mus musculus||[[Event:682#Evidence Supporting Taxonomic Applicability|Strong]]||[http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id=10090 NCBI]
  
 
|-
 
|-
  
| rat || Rattus norvegicus || [[Event:682#Evidence Supporting Taxonomic Applicability|Strong]] || [http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id=10116 NCBI]
+
|rat||Rattus norvegicus||[[Event:682#Evidence Supporting Taxonomic Applicability|Strong]]||[http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id=10116 NCBI]
 +
 
 +
|-
 +
 
 +
|guinea pig||Cavia porcellus||[[Event:682#Evidence Supporting Taxonomic Applicability|Strong]]||[http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id=10141 NCBI]
  
 
|-
 
|-
Line 52: Line 58:
  
 
!Biological Organization
 
!Biological Organization
 +
 +
|-
 +
 +
|Tissue
  
 
|-
 
|-
Line 58: Line 68:
  
 
== How this Key Event works ==
 
== How this Key Event works ==
In neuroscience, an excitatory postsynaptic potential (EPSP) is a postsynaptic potential that makes the neuron more likely to fire an action potential. This temporary depolarization of postsynaptic membrane potential, as a result of opening ligand-gated ion channels, can be caused by the flow of positively charged ions into the postsynaptic cell, or a decrease in outgoing positive charges.
+
In neuroscience, an excitatory postsynaptic potential (EPSP) is defined as a neurotransmitter-induced postsynaptic potential change that depolarizes the cell, and hence increases the likelihood of initiating a postsynaptic action potential (Purves et al. 2001). On the contrary, an inhibitory  postsynaptic potential (IPSP) decreases this likelihood. Whether a postsynaptic response is an EPSP or an IPSP depends on the type of channel that is coupled to the receptor, and on the concentration of permeant ions inside and outside the cell. In fact, the only factor that distinguishes postsynaptic excitation from inhibition is the reversal potential of the postsynaptic potential (PSP) in relation to the threshold voltage for generating action potentials in the postsynaptic cell. When an active presynaptic cell releases neurotransmitters into the synapse, some of them bind to receptors on the postsynaptic cell. Many of these receptors contain an ion channel capable of passing positively charged ions (e.g., Na+ or K+) or negatively charged ions (e.g., Cl-) either into or out of the cell. In epileptogenesis, discharges reduced GABA-A receptor-mediated hyperpolarizing IPSPs by shifting their reversal potentials in a positive direction. At the same time, the amplitudes of Schaffer collateral-evoked RS-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor-mediated EPSPs and action potential-independent miniature EPSPs were enhanced, whereas N-methyl-d-aspartate receptor-mediated EPSPs remained unchanged. Together, these changes in synaptic transmission produce a sustained increase in hippocampal excitability (Lopantsev et al. 2009).
 
+
EPSPs are graded (i.e. they have an additive effect). When multiple EPSPs occur on a single patch of postsynaptic membrane, their combined effect is the sum of the individual EPSPs. Larger EPSPs result in greater membrane depolarization and thus increase the likelihood that the postsynaptic cell reaches the threshold for firing an action potential.
+
  
 
== How it is Measured or Detected ==
 
== How it is Measured or Detected ==
<em>
+
EPSPs are usually recorded using intracellular electrodes. See Miura et al. (1997) and Bromfield et al. (2006) for details.
Methods that have been previously reviewed and approved by a recognized authority should be included in the Overview section above.
+
All other methods, including those well established in the published literature, should be described here.  
+
Consider the following criteria when describing each method:
+
1. Is the assay fit for purpose?
+
2. Is the assay directly or indirectly (i.e. a surrogate) related to a key event relevant to the final
+
adverse effect in question?
+
3. Is the assay repeatable?
+
4. Is the assay reproducible?
+
</em>
+
  
 
== Evidence Supporting Taxonomic Applicability ==
 
== Evidence Supporting Taxonomic Applicability ==
 +
Miura et al. (1997) reported supporting evidence from guinea pigs whereas Dichter and Ayala (1987) and Bromfield et al. (2006) summarized relevant studies on humans.
  
 
== References ==
 
== References ==
 +
Bromfield EB, Cavazos JE, Sirven JI. (2006) Chapter 1, Basic Mechanisms Underlying Seizures and Epilepsy. In: An Introduction to Epilepsy [Internet]. West Hartford (CT): American Epilepsy Society; Available from: http://www.ncbi.nlm.nih.gov/books/NBK2510/.
 +
 +
Dichter MA, Ayala GF. (1987) Cellular mechanisms of epilepsy: A status report. Science 237:157-64.
 +
 +
Lopantsev V, Both M, Draguhn A. 2009. Rapid Plasticity at Inhibitory and Excitatory Synapses in the Hippocampus Induced by Ictal Epileptiform Discharges. Eur J Neurosci 29(6):1153–64.
 +
 +
Miura M, Yoshioka M, Miyakawa H, Kato H, Ito KI. (1997) Properties of calcium spikes revealed during GABAA receptor antagonism in hippocampal CA1 neurons from guinea pigs. J Neurophysiol. 78(5):2269-79.
  
 +
Purves D, Augustine GJ, Fitzpatrick D, Katz LC, LaMantia A-S, McNamara JO, Williams SM (Eds). 2001. Neuroscience. 2nd edition. Chapter 7. Neurotransmitter Receptors and Their Effects. Sunderland (MA): Sinauer Associates. Available from: http://www.ncbi.nlm.nih.gov/books/NBK10799/.
 
<references />
 
<references />

Latest revision as of 14:25, 23 June 2016


Event Title

Amplified excitatory postsynaptic potential (EPSP), Generation
Amplified EPSP, Generation

Key Event Overview

Please follow link to widget page to edit this section.

If you manually enter text in this section, it will get automatically altered or deleted in subsequent edits using the widgets.

AOPs Including This Key Event

AOP Name Event Type Essentiality
Binding to the picrotoxin site of ionotropic GABA receptors leading to epileptic seizures KE Strong

Taxonomic Applicability

Name Scientific Name Evidence Links
mouse Mus musculus Strong NCBI
rat Rattus norvegicus Strong NCBI
guinea pig Cavia porcellus Strong NCBI

Level of Biological Organization

Biological Organization
Tissue

How this Key Event works

In neuroscience, an excitatory postsynaptic potential (EPSP) is defined as a neurotransmitter-induced postsynaptic potential change that depolarizes the cell, and hence increases the likelihood of initiating a postsynaptic action potential (Purves et al. 2001). On the contrary, an inhibitory postsynaptic potential (IPSP) decreases this likelihood. Whether a postsynaptic response is an EPSP or an IPSP depends on the type of channel that is coupled to the receptor, and on the concentration of permeant ions inside and outside the cell. In fact, the only factor that distinguishes postsynaptic excitation from inhibition is the reversal potential of the postsynaptic potential (PSP) in relation to the threshold voltage for generating action potentials in the postsynaptic cell. When an active presynaptic cell releases neurotransmitters into the synapse, some of them bind to receptors on the postsynaptic cell. Many of these receptors contain an ion channel capable of passing positively charged ions (e.g., Na+ or K+) or negatively charged ions (e.g., Cl-) either into or out of the cell. In epileptogenesis, discharges reduced GABA-A receptor-mediated hyperpolarizing IPSPs by shifting their reversal potentials in a positive direction. At the same time, the amplitudes of Schaffer collateral-evoked RS-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor-mediated EPSPs and action potential-independent miniature EPSPs were enhanced, whereas N-methyl-d-aspartate receptor-mediated EPSPs remained unchanged. Together, these changes in synaptic transmission produce a sustained increase in hippocampal excitability (Lopantsev et al. 2009).

How it is Measured or Detected

EPSPs are usually recorded using intracellular electrodes. See Miura et al. (1997) and Bromfield et al. (2006) for details.

Evidence Supporting Taxonomic Applicability

Miura et al. (1997) reported supporting evidence from guinea pigs whereas Dichter and Ayala (1987) and Bromfield et al. (2006) summarized relevant studies on humans.

References

Bromfield EB, Cavazos JE, Sirven JI. (2006) Chapter 1, Basic Mechanisms Underlying Seizures and Epilepsy. In: An Introduction to Epilepsy [Internet]. West Hartford (CT): American Epilepsy Society; Available from: http://www.ncbi.nlm.nih.gov/books/NBK2510/.

Dichter MA, Ayala GF. (1987) Cellular mechanisms of epilepsy: A status report. Science 237:157-64.

Lopantsev V, Both M, Draguhn A. 2009. Rapid Plasticity at Inhibitory and Excitatory Synapses in the Hippocampus Induced by Ictal Epileptiform Discharges. Eur J Neurosci 29(6):1153–64.

Miura M, Yoshioka M, Miyakawa H, Kato H, Ito KI. (1997) Properties of calcium spikes revealed during GABAA receptor antagonism in hippocampal CA1 neurons from guinea pigs. J Neurophysiol. 78(5):2269-79.

Purves D, Augustine GJ, Fitzpatrick D, Katz LC, LaMantia A-S, McNamara JO, Williams SM (Eds). 2001. Neuroscience. 2nd edition. Chapter 7. Neurotransmitter Receptors and Their Effects. Sunderland (MA): Sinauer Associates. Available from: http://www.ncbi.nlm.nih.gov/books/NBK10799/.