BS2550 Neuronal Signalling Exam Questions

Neuronal cells maintain a negative resting membrane potential (RMP) primarily due to the selective permeability of the cell membrane to different ions. The main forces driving ion distribution are the electrochemical gradient and the membrane's selective permeability.
The electrochemical gradient is the combined force of the concentration gradient and the electrical gradient.
The concentration gradient refers to the difference in ion concentration across the membrane. For example, there is a higher concentration of potassium ions (K+) inside the cell than outside, while the concentration of sodium ions (Na+) is higher outside.
The electrical gradient is the difference in electrical potential across the membrane, caused by the uneven distribution of charged ions.
The membrane's selective permeability determines which ions can move across the membrane and at what rate.
The neuron's membrane is more permeable to K+ than Na+ at rest. This means that K+ can easily flow out of the cell, driven by both the concentration gradient (more K+ inside) and the electrical gradient (the inside is negative and repels positively charged K+).
This outflow of K+ contributes to the negative RMP.
The sodium-potassium pump, although it requires energy, also plays a role in maintaining the RMP. This pump constantly moves three Na+ ions out of the cell for every two K+ ions pumped in, helping to maintain the concentration gradients and thus contributing to the negative RMP.

An axon designed for fast signal propagation typically exhibits several key features:

1. Large Diameter: A larger axon diameter reduces internal resistance, allowing for faster current flow. This is particularly important in myelinated axons, as the myelin sheath further increases the effective diameter of the axonal segment.
2. Myelination: A thick myelin sheath, composed of layers of lipid-rich Schwann cells, wraps around the axon, providing insulation and reducing capacitance. Myelination allows for saltatory conduction, where the action potential jumps from one node of Ranvier (a gap in the myelin sheath) to the next, significantly increasing conduction velocity.
3. High Membrane Resistance: The membrane resistance of the axon is determined by the tightness of the lipid bilayer and the density of ion channels. A high membrane resistance ensures that current flow is primarily through the axoplasm and not lost across the membrane, minimizing signal decay.
4. Low Internal Resistance: The internal resistance of the axon is determined by the resistivity of the axoplasm, which is largely influenced by the diameter of the axon. A lower internal resistance facilitates rapid current flow along the axon.
   These anatomical and biophysical properties work synergistically to minimize signal loss and ensure fast, efficient signal propagation across long distances, enabling rapid communication within the nervous system.

The fate of one molecule of glucose 6-phosphate (G6P) leading to calcium release from the endoplasmic reticulum (ER) involves a complex series of reactions known as the glucose 6-phosphate dehydrogenase pathway. This pathway is connected to the inositol trisphosphate (IP3) signaling pathway, a key mechanism for calcium release in cells. Here is a simplified description of the process:

1. G6P Utilization: Glucose 6-phosphate is a crucial intermediate in glucose metabolism. Its fate depends on the cell's energy needs and the availability of other metabolic substrates. For this scenario, we'll focus on its role in generating NADPH, a reducing coenzyme essential for various metabolic pathways.

2. NADPH Production: G6P proceeds through the pentose phosphate pathway. In this pathway, G6P is converted to 6-phosphogluconate, a key intermediate. This reaction generates NADPH, a reduced coenzyme playing a crucial role in reducing oxidative stress and providing substrates for biosynthetic reactions.

3. IP3 Production by Phospholipase C: The NADPH produced in step 2 can activate a critical enzyme called phospholipase C (PLC). The activation of PLC is crucial for the subsequent release of calcium.

4. Signal Transduction: PLC triggers the cleavage of phosphatidylinositol 4,5-bisphosphate (PIP2) located in the cell membrane. This cleavage releases the secondary messengers IP3 and diacylglycerol (DAG) which are important in intracellular signaling.

5. Calcium Release: IP3 binds to the IP3 receptor on the ER membrane. This binding causes the opening of the calcium channels of the ER, leading to the release of calcium ions into the cytosol.

Steps critical for cell signaling:

The activation of PLC is a critical step for cell signaling, as it links metabolism and calcium release. Its activation by NADPH demonstrates the interconnectedness of metabolic and signaling pathways.

The release of calcium from the ER is a fundamental event in cellular signaling. Calcium is a ubiquitous intracellular second messenger, and its release triggers a wide array of cellular responses, including muscle contraction, neurotransmitter release, and enzyme regulation.

Diagram:

[Diagram illustration of the pathway, showing G6P being utilized in the pentose phosphate pathway to produce NADPH, which in turn activates PLC. PLC then cleaves PIP2 to produce IP3 and DAG. IP3 binds to the IP3 receptor on the ER, leading to calcium release.]

<p>Here's a design for a novel protein that integrates calcium-dependent activation with extracellular signaling and PKA regulation:</p> <p><strong>Protein Design:</strong></p> <ol> <li> <p><strong>Extracellular Signal-Binding Domain:</strong> The protein will possess an extracellular domain that binds to a specific extracellular ligand. This domain is responsible for initiating the signaling cascade upon ligand binding.</p> </li> <li> <p><strong>Calmodulin-Binding Domain (CaMBD):</strong> This domain is designed to bind to calmodulin (CaM), a calcium-binding protein. CaM undergoes conformational changes upon binding calcium, enabling it to interact with target proteins.</p> </li> <li> <p><strong>Protein Kinase A (PKA) Regulatory Subunit-Binding Domain:</strong> This domain is designed to interact with the regulatory subunit of PKA. When bound, PKA is inactive.</p> </li> <li> <p><strong>Calcium-Dependent Conformational Change:</strong> The design incorporates a mechanism where binding of the extracellular ligand to the signal-binding domain causes a conformational change within the protein. This conformational change, however, is only fully activated in the presence of calcium.</p> </li> </ol> <p><strong>Activation Pathway:</strong></p> <ol> <li> <p><strong>Ligand Binding:</strong> An extracellular ligand binds to the signal-binding domain.</p> </li> <li> <p><strong>Conformational Change:</strong> The protein undergoes a conformational change, partially exposing the CaMBD.</p> </li> <li> <p><strong>Calcium Binding:</strong> Calcium ions bind to CaM, inducing further conformational changes in the protein. The interaction between the CaMBD and CaM-calcium is essential for full activation.</p> </li> <li> <p><strong>PKA Activation:</strong> The conformational changes induced by calcium facilitate the binding of the protein to the regulatory subunit of PKA. This binding disrupts the association of the regulatory subunit with the catalytic subunit, allowing the catalytic subunit of PKA to become active.</p> </li> <li> <p><strong>Downstream Signaling:</strong> The activated catalytic subunit of PKA can phosphorylate target proteins, altering cellular processes like enzyme activation, gene expression, and cell growth.</p> </li> </ol> <p><strong>Benefits:</strong></p> <p>This design allows for a more specific and regulated activation of PKA, ensuring that it is only activated in response to both an extracellular signal and the presence of calcium. This precise control mechanism is crucial for preventing unwanted activation of PKA and ensuring appropriate cellular responses to specific stimuli.</p> Signup and view all the answers