Dopamine is a neurotransmitter that helps control the brain\'s reward and pleasu

Question

Dopamine is a neurotransmitter that helps control the brain's reward and pleasure centers. It has been implicated in many diseases such as depression, bipolar disorder, Parkinson's, ADHD, and many others. Dopamine levels inside and outside the cell are controlled by dopamine transporters, which, ironically enough, transport dopamine across cell membranes. These transporters bring dopamine inside the cell. Medications used to control these disorders (such as Adderall, Ritalin, and Wellbutrin) target the transporter, as do many addictive drugs (cocaine and amphetamines). Thus dopamine transporters are a hot research topic. You are studying cells that have a dopamine transporter on its cell surface. You initially place these cells in a high salt buffer (lots of salt outside the cells), and you don't see any evidence of dopamine transport. This is a problem. So you play around with the salt concentration and find that transport occurs much more efficiently when there is a low amount of salt in the buffer. What can you hypothesize about the concentrations of dopamine inside versus outside the cell, and what facilitates this transport? a. b. The dopamine is bound in an active site through two aspartic acid residues as shown below. After dopamine binding, a gate composed of amino ac?ds is closed preventing the dopamine to release back where it came from. Sodium ions then bind in to the transporter, which causes release of the dopamine. What is holding the dopamine in place? Why would an influx of sodium ions into this structure cause dopamine to be dislodged?

Explanation / Answer

The function of Dopamine transporters is to transport dopamine inside the cell.

a. From the given data, it can be seen that -

This shows that dopamine transport occurs along with the osmosis gradient of water present in the cell. When there is low salt concentration outside the cell, water travels from outside to inside (low salt to high salt). Dopamine transportation occurs in the same direction. The fact that in the case of high salt concentration outside the cell, water travels from inside the cell to outside and no dopamine transport takes place inside the cell, affirms this hypothesis. Furthermore, these gradients are caused by neuromodulatory mechanisms.

b. Dopamine is held in a bound state because of its conformation. This particular conformation allows dopamine to be bound by aspartic acid residues in place. Because of influx of sodium ions, the conformation of dopamine changes, which breaks the aspartic acid bonds, and causes the release of dopamine.

c. The transporter works so efficiently in one direction because of binding of dopamine by the aspartic acid residues in place and the low salt concentration in the cell. The transporter requires other factors to come in play apart from the salt concentration for a reverse function, for example the concentration of dopamine inside the cell, influx of potassium ions, etc.

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