Ionotropic GABA receptor: Difference between revisions

Add links
From Wikipedia, the free encyclopedia
Browse history interactively
← Previous editNext edit →
Content deleted Content added
VisualWikitext
No edit summary
I added an introduction to synapses, a section about the difference between ionotropic and metabotropic GABA receptors and a section about the pharmacological implications of the characterization of iGABAR receptors. ~~~~
Line 4: Line 4:
* [[GABAA-rho receptor|GABA<sub>A</sub>-ρ receptor]]
* [[GABAA-rho receptor|GABA<sub>A</sub>-ρ receptor]]


The [[GABAB receptor|GABA<sub>B</sub> receptor]], a [[G protein-coupled receptor]], is the only ''[[metabotropic]]'' GABA receptor.
The [[GABAB receptor|GABA<sub>B</sub> receptor]], a [[G protein-coupled receptor]], is the only ''[[metabotropic]]'' GABA receptor.

They belong to a larger class of GABA receptors which are known for their inhibitory effects on postsynaptic cells. There are physiological differences between the ionotropic and metabotropic GABA receptors.There are pharmacological implications in characterizing iGABAR receptors.

=== Introduction ===
[[File:Neuromuscular_junction.svg|link=https://en.wikipedia.org/wiki/File:Neuromuscular_junction.svg|thumb|This is a neuromuscular junction. There is a presynaptic unit (axon), a synapse and a postsynaptic unit (dendrite). Neurotransmitters are released into the synapse.]]
The neuromuscular junction in the CNS can be composed of a presynaptic unit located at an axon terminal with synaptic vesicles and a postsynaptic unit located at a dendrite.<ref>{{Cite journal|title=Synaptic transmission|url=http://accessscience.com/content/674100|language=en|doi=10.1036/1097-8542.674100}}</ref> Neurotransmitters are chemical molecules that are released from a presynaptic unit into the synapse and received by the postsynaptic unit, resulting in a biological and electrophysiological effect. The two main types of neurotransmitters are amino acid transmitters and GABA transmitters.<ref>{{Cite journal|title=Synaptic transmission|url=http://accessscience.com/content/674100|language=en|doi=10.1036/1097-8542.674100}}</ref> The release of and binding of glutamate, an amino acid transmitter, to its respective receptor manifests in an [[excitatory postsynaptic potential]] (EPSP).<ref>{{Cite journal|title=Synaptic transmission|url=http://accessscience.com/content/674100|language=en|doi=10.1036/1097-8542.674100}}</ref> On the other hand, the release and binding of gamma-amino butyric acid (GABA) to the GABA receptor results in an [[Inhibitory postsynaptic potential|inhibitory postynaptic potential]] (IPSP).<ref>{{Cite journal|title=Synaptic transmission|url=http://accessscience.com/content/674100|language=en|doi=10.1036/1097-8542.674100}}</ref> The ability of the GABA receptor function rests on its molecular structure of multiple binding sites and conductance levels.<ref>{{Cite journal|title=Synaptic transmission|url=http://accessscience.com/content/674100|language=en|doi=10.1036/1097-8542.674100}}</ref> These receptors are prevalent in interneurons relaying messages among various regions of the brain.<ref>{{Cite journal|title=Synaptic transmission|url=http://accessscience.com/content/674100|language=en|doi=10.1036/1097-8542.674100}}</ref>

=== The Difference Between Ionotropic and Metabotropic GABA receptors ===
[[File:Classification_of_Ligand-Gated_Ion_Channels_2.jpg|link=https://en.wikipedia.org/wiki/File:Classification_of_Ligand-Gated_Ion_Channels_2.jpg|thumb|Classification of Ligand-Gated Ion Channels: iGABARs fall under the [[Cys-loop receptor|Cys-Loop receptors]].]]
The two types of [[GABA receptor|GABA receptors]] are the [[GABAA receptor|GABA<sub>A</sub>]] and [[GABAB receptor|GABA<sub>B</sub>]] receptors. The pentameric GABA<sub>A</sub> receptors are [[Ligand-gated ion channel|ionotropic]], meaning that upon binding with the ligand their biological and electrophysiological effect is carried out through the conductance of ions.<ref>{{Cite book|last=Enna, S. J. Möhler, Hanns|url=http://worldcat.org/oclc/474809970|title=The GABA receptors|date=2007|publisher=Humana Press|oclc=474809970}}</ref> This is why the physiological makeup for GABA<sub>A</sub> receptors differs from GABA<sub>B</sub> in that they are [[Ligand-gated ion channel|ligand-gated ion channels]]. The chloride-ion gated channels facilitate the inhibitory effect through the influx of chloride ions.<ref>{{Cite book|last=Enna, S. J. Möhler, Hanns|url=http://worldcat.org/oclc/474809970|title=The GABA receptors|date=2007|publisher=Humana Press|oclc=474809970}}</ref> However, GABA<sub>B</sub> receptors are metabotropic meaning they utilize a G-protein coupled mechanism. Since the G-protein is a [[heterodimeric]]<ref>{{Cite book|last=Enna, S. J. Möhler, Hanns|url=http://worldcat.org/oclc/474809970|title=The GABA receptors|date=2007|publisher=Humana Press|oclc=474809970}}</ref> molecule, the separation and phosphorylation of its parts result in a [[signal cascade]], resulting in a more steady but amplified response. 

=== Pharmacological Implications ===
Earlier a third type of GABA receptor was discovered and named GABA<sub>C</sub>, but recently it has been categorized as a [[GABAA-rho receptor|sub-type of the GABA<sub>A</sub> receptor]]<ref>{{Cite journal|last=Bormann|first=Joachim|date=2000-01-01|title=The ‘ABC’ of GABA receptors|url=https://www.cell.com/trends/pharmacological-sciences/abstract/S0165-6147(99)01413-3|journal=Trends in Pharmacological Sciences|language=English|volume=21|issue=1|pages=16–19|doi=10.1016/S0165-6147(99)01413-3|issn=0165-6147|pmid=10637650}}</ref>. Thus, the iontropic GABA receptors consist of the GABA<sub>A</sub> receptor and the [[GABAA-rho receptor|GABA<sub>A</sub>-ρ receptor]].There are pharmacological implications in understanding the molecular structure and function of these ionotropic receptors. Since they are targeted by neuroactive drugs, this characteristic is exploited in order to deduce their molecular structure and function in the CNS.<ref>{{Cite journal|last=Palyulin|first=Vladimir A|last2=Radchenko|first2=EV|last3=Osolodkin|first3=DE|last4=Chupakhin|first4=VI|last5=Zefirov|first5=NS|date=2010-05|title=Ionotropic GABA receptors: modelling and design of selective ligands|url=http://dx.doi.org/10.1186/1758-2946-2-s1-p49|journal=Journal of Cheminformatics|volume=2|issue=S1|doi=10.1186/1758-2946-2-s1-p49|issn=1758-2946}}</ref> For example, GABA<sub>A</sub> receptors respond to neuroactive drugs like [[Benzodiazepine|bensodiazepines]]<ref>{{Cite journal|title=Tranquilizer|url=http://accessscience.com/content/704300|language=en|doi=10.1036/1097-8542.704300}}</ref>. Normally increasing a neuron's permeability to chloride ions results in inhibition; bensodiazepines further propagate this event ensuring inhibition, serving as an indirect<ref>{{Cite journal|title=Tranquilizer|url=http://accessscience.com/content/704300|language=en|doi=10.1036/1097-8542.704300}}</ref> factor. Armed with the knowledge of chloride ion permeability leading to inhibition, it is important to note that ethanol and barbiturates<ref>{{Cite journal|title=Tranquilizer|url=http://accessscience.com/content/704300|language=en|doi=10.1036/1097-8542.704300}}</ref> can directly increase the influx of chloride ions resulting in inhibition. Further characterization of the [[Allosteric regulation|allosteric]] modulations<ref>{{Cite journal|date=2007|editor-last=Enna|editor-first=S. J.|editor2-last=Möhler|editor2-first=Hanns|title=The GABA Receptors|url=http://dx.doi.org/10.1007/978-1-59745-465-0|journal=The Receptors|doi=10.1007/978-1-59745-465-0}}</ref> of the active sites in the ionotropic gives insight on new treatments and nervous system disorders, such as panic disorder<ref>{{Cite journal|title=Anxiety disorders|url=http://accessscience.com/content/042250|language=en|doi=10.1036/1097-8542.042250}}</ref>.


==References==
==References==

Revision as of 10:23, 26 April 2020

Ionotropic GABA receptors (iGABARs) are ligand-gated ion channel GABA receptors and include:

The GABAB receptor, a G protein-coupled receptor, is the only metabotropic GABA receptor.

They belong to a larger class of GABA receptors which are known for their inhibitory effects on postsynaptic cells. There are physiological differences between the ionotropic and metabotropic GABA receptors.There are pharmacological implications in characterizing iGABAR receptors.

Introduction

This is a neuromuscular junction. There is a presynaptic unit (axon), a synapse and a postsynaptic unit (dendrite). Neurotransmitters are released into the synapse.

The neuromuscular junction in the CNS can be composed of a presynaptic unit located at an axon terminal with synaptic vesicles and a postsynaptic unit located at a dendrite.[1] Neurotransmitters are chemical molecules that are released from a presynaptic unit into the synapse and received by the postsynaptic unit, resulting in a biological and electrophysiological effect. The two main types of neurotransmitters are amino acid transmitters and GABA transmitters.[2] The release of and binding of glutamate, an amino acid transmitter, to its respective receptor manifests in an excitatory postsynaptic potential (EPSP).[3] On the other hand, the release and binding of gamma-amino butyric acid (GABA) to the GABA receptor results in an inhibitory postynaptic potential (IPSP).[4] The ability of the GABA receptor function rests on its molecular structure of multiple binding sites and conductance levels.[5] These receptors are prevalent in interneurons relaying messages among various regions of the brain.[6]

The Difference Between Ionotropic and Metabotropic GABA receptors

Classification of Ligand-Gated Ion Channels: iGABARs fall under the Cys-Loop receptors.

The two types of GABA receptors are the GABAA and GABAB receptors. The pentameric GABAA receptors are ionotropic, meaning that upon binding with the ligand their biological and electrophysiological effect is carried out through the conductance of ions.[7] This is why the physiological makeup for GABAA receptors differs from GABAB in that they are ligand-gated ion channels. The chloride-ion gated channels facilitate the inhibitory effect through the influx of chloride ions.[8] However, GABAB receptors are metabotropic meaning they utilize a G-protein coupled mechanism. Since the G-protein is a heterodimeric[9] molecule, the separation and phosphorylation of its parts result in a signal cascade, resulting in a more steady but amplified response. 

Pharmacological Implications

Earlier a third type of GABA receptor was discovered and named GABAC, but recently it has been categorized as a sub-type of the GABAA receptor[10]. Thus, the iontropic GABA receptors consist of the GABAA receptor and the GABAA-ρ receptor.There are pharmacological implications in understanding the molecular structure and function of these ionotropic receptors. Since they are targeted by neuroactive drugs, this characteristic is exploited in order to deduce their molecular structure and function in the CNS.[11] For example, GABAA receptors respond to neuroactive drugs like bensodiazepines[12]. Normally increasing a neuron's permeability to chloride ions results in inhibition; bensodiazepines further propagate this event ensuring inhibition, serving as an indirect[13] factor. Armed with the knowledge of chloride ion permeability leading to inhibition, it is important to note that ethanol and barbiturates[14] can directly increase the influx of chloride ions resulting in inhibition. Further characterization of the allosteric modulations[15] of the active sites in the ionotropic gives insight on new treatments and nervous system disorders, such as panic disorder[16].

References

  1. ^ "Synaptic transmission". doi:10.1036/1097-8542.674100. {{cite journal}}: Cite journal requires |journal= (help)
  2. ^ "Synaptic transmission". doi:10.1036/1097-8542.674100. {{cite journal}}: Cite journal requires |journal= (help)
  3. ^ "Synaptic transmission". doi:10.1036/1097-8542.674100. {{cite journal}}: Cite journal requires |journal= (help)
  4. ^ "Synaptic transmission". doi:10.1036/1097-8542.674100. {{cite journal}}: Cite journal requires |journal= (help)
  5. ^ "Synaptic transmission". doi:10.1036/1097-8542.674100. {{cite journal}}: Cite journal requires |journal= (help)
  6. ^ "Synaptic transmission". doi:10.1036/1097-8542.674100. {{cite journal}}: Cite journal requires |journal= (help)
  7. ^ Enna, S. J. Möhler, Hanns (2007). The GABA receptors. Humana Press. OCLC 474809970.{{cite book}}: CS1 maint: multiple names: authors list (link)
  8. ^ Enna, S. J. Möhler, Hanns (2007). The GABA receptors. Humana Press. OCLC 474809970.{{cite book}}: CS1 maint: multiple names: authors list (link)
  9. ^ Enna, S. J. Möhler, Hanns (2007). The GABA receptors. Humana Press. OCLC 474809970.{{cite book}}: CS1 maint: multiple names: authors list (link)
  10. ^ Bormann, Joachim (2000-01-01). "The 'ABC' of GABA receptors". Trends in Pharmacological Sciences. 21 (1): 16–19. doi:10.1016/S0165-6147(99)01413-3. ISSN 0165-6147. PMID 10637650.
  11. ^ Palyulin, Vladimir A; Radchenko, EV; Osolodkin, DE; Chupakhin, VI; Zefirov, NS (2010-05). "Ionotropic GABA receptors: modelling and design of selective ligands". Journal of Cheminformatics. 2 (S1). doi:10.1186/1758-2946-2-s1-p49. ISSN 1758-2946. {{cite journal}}: Check date values in: |date= (help)CS1 maint: unflagged free DOI (link)
  12. ^ "Tranquilizer". doi:10.1036/1097-8542.704300. {{cite journal}}: Cite journal requires |journal= (help)
  13. ^ "Tranquilizer". doi:10.1036/1097-8542.704300. {{cite journal}}: Cite journal requires |journal= (help)
  14. ^ "Tranquilizer". doi:10.1036/1097-8542.704300. {{cite journal}}: Cite journal requires |journal= (help)
  15. ^ Enna, S. J.; Möhler, Hanns, eds. (2007). "The GABA Receptors". The Receptors. doi:10.1007/978-1-59745-465-0.
  16. ^ "Anxiety disorders". doi:10.1036/1097-8542.042250. {{cite journal}}: Cite journal requires |journal= (help)



Stub icon

This biochemistry article is a stub. You can help Wikipedia by expanding it.

Retrieved from "https://en.wikipedia.org/w/index.php?title=Ionotropic_GABA_receptor&oldid=953233681"