Chemical Neurotransmission

1. What are important players of chemical neurotransmission?

1. Second messengers

2. 7 transmembrane region G protein linked

3. 4 transmembrane region ligand gated ion channel

4. 12 transmembrane region transporter

1. What are intracellular chemicals produced when some neurotransmitters bind to their receptor and are capable of converting the binding information of their neurotransmitter into the synthesis of these chemicals?

Second messengers

1. What is the other name of ionotropic receptors?

1. Ligand-gated ion channel

1. What determines if the ionotropic receptor is open?

1. If the neurotransmitter (ligand) binds and allows ions to travel into the cell

1. What are the different parts of the ion channel?

1. Ion channel

   1. pore

2. Cell membrane

3. Ion filter

4. Gate

1. How does the gate determine what enters the ion channel?

1. Charge 

2. Size

1. What can ion channels be?

1. ligand -gated 

   1. Opened and closed by NT ligands

2. Voltage-gated

   1. Opened and closed by the voltage charge across the channel

1. Describe the way in which GABA enters the neuron

1. Action potential

2. Ca2+ entry 

3. Vesicle releases NT

   1. GABA 

   2. Glycine

1. GABA goes through either ionotropic receptor or metabotropic receptor

   1. A

      1. Ionotropic receptor

         1. ligand-gated

         2. 5 subunit

         3. Fast-onset

         4. Drive Cl into cell

         5. Calms cell activity

   2. B

      1. Metabotropic

         1. G-protein coupled receptor

         2. Slow onset

         3. Drives K+ potassium out of the cell

         4. Long lasting dampening effect on cell activity

1. What is another name for a metabotropic receptor?

1. G protein-coupled receptor

   1. Crosses membrane 7 times

1. Describe the arrangement of the metabotropic receptor.

1. The seven transmembrane regions are not arranged in a line but rather in a circle

2. Middle of this circle is a central core

1. Where is the binding site for neurotransmitters on a metabotropic receptor?

1. In the central core

1. What are the 4 elements that comprise the second messenger system?

1. Neurotransmitter

   1. First Messenger

2. NT receptor 

3. G protein

4. Enzyme

   1. Synthesizes the second messenger

1. What is the job of the 1st messenger for a G-protein coupled receptor?

1. Transform the receptor in order to make it capable of binding the G protein

   1. Require conformation change of the neurotransmitter receptor

1. What do the beta and gamma subunit do as part of the GTPy(gamma)S Assay?

1. Inhibit each other and when dissociated the are activated

1. Are g-protein coupled receptors slower than ligand gated receptors?

1. Yes

1. What are the effects of the effector system?

1. Hyperpolarizes membrane

2. Every time activate, active secondary messengers change gene transcription through a cascade of events and ultimately activates transcription factor

   1. Protein moves into nucleus and bins to sequence of DNA and induce transcription into RNA and protein

1. In the Effector system, does the second messenger tell the enzyme to do?

1. To open an ion channel, allowing calcium to enter the cell

1. Describe the process of the effector system.

1. Once second messenger has been synthesized, it can continue the information transfer by further molecular conversation

   1. It is synthesized by the blue NT binding extracellularly and cascading the transfer of blue information through receptor, G protein, and enzyme to produce a second messenger.

   2. Image to top right shows the second messenger activating an intracellular enzyme.

      1. Ion channel is closed, no information is being directed at the cell’s DNA 

2. Consequence of activation of intracellular enzymes by second messenger is that some activated enzymes can instruct ion channels to open.

   1. This is mediated by a complicated molecular cascade, set in motion by second messenger activating an intracellular enzyme, which itself creates still further molecular instructions to an ionic gatekeeper to open the ion channel

1. What does the third messenger kinase do in the effector system?

1. Puts phosphates on critical proteins like ligand gated ion channels, voltage-gated ion channel, and regulatory enzymes

1. What do third messenger phosphatases do?

1. Undo what kinases create

   1. Take off phosphates from critical proteins like ligand gated ion channel, voltage gated ion channel, and regulatory enzymes

1. What enzyme is responsible for using energy?

1. ATPase

1. What are the three important classes of enzymes that regulate gene expression?

1. Active and inactive forms of protein kinases

2. Various dephosphatases

   1. Reverse actions of protein kinases

3. RNA polymerase

   1. Catalyze the transcription of DNA into RNA

1. What are examples of second messengers?

1. ATPase

2. Protein kinase

3. Phosphatase

4. RNA polymerase

1. Describe the gene regulation by neurotransmitters.

1. Neurotransmitters begin the process by activating genes by producing a second messenger

2. The second messenger activates an intracellular enzyme, protein kinase.

   1. While inactive it is paired with another copy of the enzyme plus two regulatory units

   2. To copies of the second messenger interact with the regulatory units, dissociating them from the copies of protein kinase. This activates protein kinase, readying the enzyme to phosphorylate other proteins

3. Once activated, protein kinase phosphorylates a transcription factor. Attacking PO3 to this transcription factor activates it so it can bind to the regulatory region of a gene

4. Activated transcription factor noe binds to the regulatory region of the gene and activates it. Gene shown is cFOs. Activation of a gene means that it is transcribed into RNA and then the RNA is translated into the protein for which it codes

   1. Protein is Fos from the gene cFos

5. Continuous cascade from the 1st messenger neurotransmitter to the gene activation and production of the gene product, Fos protein

1. How fast do immediate early genes act?

1. Fast upon activation

   1. RNA

      1. 1-2 hours

   2. Proteins

      1. 3-6 hours

1. How do early genes activate late genes?

1. A transcription factors is activating the immediate early gene cFos and producing the protein product Fos

2. While the cFos gene is being activated another immediate early gene is being simultaneously activated. This second gene is called cJun and it is producing its protein product Jun

3. Once Fos and Jun proteins are synthesized they can collaborate as partners and produce Fos-Jun combination protein, which now acts as a transcription factor for late genes. Sometimes the Fos-Jun transcription factor is called a leucine zipper

4. Leucine zipper transcription factor formed by the products of the activated early genes cFos and cJun now returns to the genome and finds another gene. Since this gene is activated later than the others, it is called a late gene. Thus, early genes activate late genes when the products of early genes are themselves transcription factors. The product of the late gene can be any protein the neuron needs, such as an enzyme transport, or growth factor.

5. Immediate early genes cFos and cJun are expressed, and their protein product Fod and Jun are formed. NExt, a transcription factor, namely a leucine zipper, is created by the cooperation of Fos and Jun together. FInally, this transcription factor goes on to activate a late gene, resulting in the expression of its own gene product