User:ProfAccount1/CHRNA6: Difference between revisions – Wikipedia

 

Line 28: Line 28:

}}</ref>

}}</ref>

”’α6”’ ”’nAChRs are expressed”’ ”’on”’ [[Dopamine|”’dopamine”’]], glutamine [[Glutamine|glutamine]], [[Norepinephrine|noradrenaline]], and [[GABA]]”’-releasing neurons,”’ but their expression patterns vary between different types of neurons.<ref>{{cite journal

”’α6”’ ”’nAChRs are expressed”’ ”’on”’ [[Dopamine|”’dopamine”’]], [[Glutamine|glutamine]], [[Norepinephrine|noradrenaline]], and [[GABA]]”’-releasing neurons,”’ but their expression patterns vary between different types of neurons.<ref>{{cite journal

|last1=Hajy Heydary

|last1=Hajy Heydary

|first1=Yasamin

|first1=Yasamin

This is the sandbox page where you will draft your initial Wikipedia contribution. If you’re starting a new article, you can develop it here until it’s ready to go live. If you’re working on improvements to an existing article, copy only one section at a time of the article to this sandbox to work on, and be sure to use an edit summary linking to the article you copied from. Do not copy over the entire article. You can find additional instructions here. Remember to save your work regularly using the “Publish page” button. (It just means ‘save’; it will still be in the sandbox.) You can add bold formatting to your additions to differentiate them from existing content.

Tissue Distribution:

α6-containing nicotinic acetylcholine receptors (nAChRs) show a restricted expression pattern in the brain. Neural nicotinic acetylcholine receptors containing α6 subunits are primarily expressed in three regions: the Ventral Tegmental Area (VTA) and the Substantia Nigra (SN), which are both part of the midbrain dopaminergic system, and the Locus Coeruleus (LC), located in the brainstem.^[1]

α6 nAChRs are expressed on dopamine, glutamine, noradrenaline, and GABA-releasing neurons, but their expression patterns vary between different types of neurons.^[2]

α6 subunits cannot form homomeric receptors. Instead, they form heteromeric receptors along with other alpha or beta subunits. Different combinations of subunits create receptors with different kinetics and affinity for ACh and nicotine.^[3]

Function:

α6 nACh receptors play a key role in regulating dopaminergic neurotransmission.

==Nicotine==

In the presence of nicotine, α6 nAChRs activate dopamine release in the VTA. This appears to takes place through two mechanisms.

First, nicotine binds to α6 nAChRs on presynpatic GABAergic neurons which connect to postsynaptic dopaminergic neurons. These receptors are quickly desensitized by nicotine, which prevents Ca2+ from entering the cell. As a result, less GABA is released. Dopaminergic neurons are no longer inhibited, leading to more dopamine release.^[4][5]

Second, nicotine binds to and opens α6 nAChRs on dopaminergic neurons. In the cell body, this creates excitatory graded potentials which cause the dopaminergic cells to fire more often. In the axon terminal, this allows Ca2+ to enter, facilitating neurotransmitter release. As a result, these neurons release more dopamine.^[6][7]

Dopamine release following activation of these neurons is thought to be involved in the addictive properties of nicotine. Studies in mice show that knocking out the α6 subunit causes mice to stop self-administering nicotine, while reintroducing the subunit reverses this result.^[8][9]

Subheading: Ethanol

In the VTA, low levels of ethanol increase dopamine release. Ethanol acts as a positive allosteric modulator by binding to α6 nAChRs on the axon terminals of GABAergic neurons outside the VTA, which are connected to other GABAergic neurons in the VTA. This modulation enhances the conductance of these neurons, leading to increased GABA release onto VTA neurons. The excess GABA inhibits the GABAergic neurons in the VTA, reducing their ability to suppress dopaminergic neurons. As a result, there is a net increase in dopamine release within the VTA.^[10][11]

However, very high levels of ethanol actually reduce dopamine release. The exact mechanism for this is unknown.^[12][13]

Research in animals has implicated α6-containing nAChRs in the abusive and addictive properties of ethanol, with mecamylamine demonstrating a potent ability to block these properties.

Minor adjustment to the Clinical Significance section:

Because of their selective distribution and role in dopamine regulation in the Substantia Nigra, α6-containing receptors have been investigated as therapeutic targets. Due to their selective localisation on dopaminergic neurons, α6-containing nACh receptors have also been suggested as a possible therapeutic target for the treatment of Parkinson’s disease.