Neurobiology Flashcards
Lecture 1 - 6
1
Q
What are the key components of the sensory and motor systems?
A
- Sensory system: Includes sense organs, sensory nerves, and central sensory areas.
- Motor system: Includes motor neurons, central motor areas, and all muscles and ducted glands in the body.
2
Q
What are the primary functions of the nervous system?
A
The nervous system has three main functions:
- Receive and interpret sensory information about the body’s internal and external environment (sensory system).
- Make decisions based on sensory input and memory (integrating system).
- Organize and execute actions (motor system).
3
Q
What is the neuron doctrine, and who contributed to it?
A
The neuron doctrine states that neurons are the structural and functional units of the nervous system and are individual cells, not continuous with other neurons. It was developed by Golgi and Cajal, who won the Nobel Prize in 1906.
4
Q
What are the main parts of a neuron and their functions?
A
Dendrites: Increase surface area and receive inputs.
Cell body (soma): Processes incoming signals.
Axon: Carries information over distances.
Myelin: Insulates the axon to improve conduction.
Terminals: Release neurotransmitters and form synapses with other neurons.
5
Q
How are neurons classified?
A
A: Neurons can be classified by:
Morphology: E.g., multipolar, unipolar.
Function: E.g., interneurons, principle neurons.
Neurotransmitter type: E.g., cholinergic, glutamatergic, GABAergic.
6
Q
What is axonal transport, and how does it work?
A
Axonal transport moves materials between the soma and axon terminals.
Anterograde transport: Moves materials from the soma to terminals (fast: 300–400 mm/day, slow: 5–10 mm/day).
Retrograde transport: Moves materials from terminals to the soma (150–200 mm/day).
Requires ATP hydrolysis and microtubules.
7
Q
What roles do glial cells play in the nervous system?
A
Form the myelin sheath.
Maintain the ionic environment.
Mop up neurotransmitters.
Provide metabolic support to neurons.
Clean up cellular debris and launch immune responses.
8
Q
How did nervous systems evolve in animals?
A
Nervous systems evolved from simple nerve nets to more complex structures like ganglia and fused ganglia, leading to the development of the brain and nerve cords in vertebrates.
9
Q
What are the key features of the human central nervous system (CNS)?
A
The CNS includes:
Brain: Divided into forebrain, midbrain, and hindbrain.
Spinal cord: Organized into segments (cervical, thoracic, lumbar, sacral) and contains gray matter (cell bodies) and white matter (axons).
10
Q
What is cerebrospinal fluid (CSF), and what are its functions?
A
CSF is a clear fluid that:
Cushions the brain and spinal cord.
Supplies nutrients and removes waste.
Buffers changes in blood pressure.
Maintains buoyancy for the brain.
It is produced by the choroid plexuses in the brain’s ventricles.
11
Q
What are the main regions of the brain and their functions?
A
Forebrain (telencephalon, diencephalon): Controls sensory integration, memory, and homeostasis.
Midbrain: Processes visual and auditory information.
Hindbrain (pons, medulla, cerebellum): Controls balance, motor control, and vital functions like respiration.
12
Q
What are the meninges, and what is their role?
A
The meninges are three protective layers surrounding the brain and spinal cord:
Dura mater: Tough outer layer.
Arachnoid mater: Middle layer with web-like structures.
Pia mater: Thin inner layer that adheres to the brain and spinal cord.
13
Q
How can we study the brain, and what are the two main approaches?
A
Bottom-up approach: Start by understanding neurons and circuits, then move to behavior.
Top-down approach: Develop theories of brain function and then investigate underlying mechanisms.
14
Q
What is the resting membrane potential of a neuron?
A
The resting membrane potential is approximately -70 mV, maintained by ionic concentration gradients and the semi-permeable cell membrane.
15
Q
What happens during hyperpolarization and depolarization?
A
Hyperpolarization makes the membrane potential more negative, while depolarization makes it less negative (more positive).
16
Q
What is the main contributor to the resting potential in neurons?
A
The potassium (K⁺) concentration gradient across the membrane, as the membrane is most permeable to K⁺.
17
Q
What is the role of the Na⁺/K⁺ ATPase pump in neurons?
A
It maintains ionic gradients by pumping 3 Na⁺ ions out and 2 K⁺ ions in, using ATP.
18
Q
How does the Nernst equation relate to membrane potential?
A
It calculates the equilibrium potential for an ion based on its concentration gradient across the membrane.
19
Q
What triggers an action potential?
A
Depolarization reaching the threshold potential (~ -55 mV) triggers the opening of voltage-gated Na⁺ channels.
20
Q
What occurs during the rising phase of an action potential?
A
Voltage-gated Na⁺ channels open, allowing Na⁺ influx, leading to further depolarization.
21
Q
What causes repolarization of the membrane after an action potential?
A
Inactivation of Na⁺ channels and opening of voltage-gated K⁺ channels, allowing K⁺ efflux.
22
Q
What is the refractory period, and why is it important?
A
The refractory period is when neurons cannot fire another action potential, ensuring unidirectional propagation of the signal.
23
Q
What are the two types of refractory periods?
A
- Absolute refractory period: No action potential possible due to inactivated Na⁺ channels.
- Relative refractory period: Requires a stronger stimulus to overcome increased K⁺ permeability.
24
Q
How does axon diameter affect conduction velocity?
A
Larger axon diameter reduces resistance, resulting in faster conduction velocity.
25
What is saltatory conduction?
In myelinated axons, action potentials jump between Nodes of Ranvier, greatly increasing conduction velocity.
26
What percentage of the brain's ATP is used for maintaining ionic gradients and synaptic transmission?
Approximately 32% for ionic gradients and 43% for synaptic transmission.
27
Why do neurons need ATP over the long term?
To maintain and restore ionic gradients via the Na⁺/K⁺ ATPase pump, essential for membrane potential and action potential generation.
28
What ensures action potentials remain all-or-none events?
Once the threshold potential is reached, the size and amplitude of the action potential are always the same, ensuring reliability.
29
What is a synapse?
Junction where information is passed
from one neuron to another.
30
Describe electrical synapses in terms of delay, direction and plasticity.
no delay
can be two-way
little plasticity
31
Describe chemical synapses. Include delay, direction, and plasticity.
Chemical released from presynaptic
neuron to modulate postsynaptic neuron (or muscle).
delay (at least 0.5 ms)
one-way
plastic (history dependent)
32
How wide is a synaptic cleft?
20-40 nm wide.
33
Describe the size of vesicles and what it contains.
40 - 50 nm diameter containing neurotransmitters.
34
Name 2 types of amino acid chemical neurotransmitters.
GABA, glutamate.
35
Describe amine chemical neurotransmitters.
Noradrenaline, dopamine, Serotonin.
36
Name neuroactive peptides that are chemical neurotransmitters.
Orexin, VIP, neurotensin, CCK.
37
How is neurotransmitter packaged in vesicles?
A non-peptide neurotransmitter is
synthesized in the nerve terminal
and transported into a vesicle.
38
What are the 4 basic steps of neurotransmitter release?
1. Docking/priming
2. Ca2+ entry
3. Vesicle fusion (exocytosis)
4. Recycling of vesicles (endocytosis)
39
Describe the docking of vesicles to the membrane.
A combination of SNAP and SNARE proteins anchor vesicles to the presynaptic membrane.
Docked vesicles are ready to release their contents.
40
Describe the process of Ca2+ entry to nerve terminals.
The action potential:
1) depolarises nerve terminal via voltage-gated Na+ channels
2) opens voltage-gated Ca2+ channels
3) Ca2+ moves into the nerve terminal down its electrochemical gradient into the neuron.
41
Describe Ca2+ entry leads to fusion of docked vesicles and release of neurotransmitter (exocytosis).
Ca2+ binds to one of the SNARE proteins (synaptotagmin, is the Ca2+ sensor).
42
Describe endocytosis (vesicle recycling).
Blocking endocytosis (eg with Dynasore, which inhibits dynamin) leads to rapid synaptic depression.
43
What does neurotransmitter do after its released?
Binds to postsynaptic receptors and produces cellular effects.
44
Name 5 compulsory qualities that a substance needs to be called a neurotransmitter.
1. Must be synthesised in the neuron
2. Show activity-dependent release from terminals
3. Duplicate effects of stimulation when applied exogenously
4. Actions blocked by competitive antagonists in a concentration-dependent manner
5. Be removed from the synaptic cleft by specific mechanisms.
45
Describe the evidence that exists to show that acetylcholine is a neurotransmitter.
1. Must be synthesised in the neuron - CHAT present in neurons
2. Show activity-dependent release from terminals - Vagusstoff
3. Duplicate effects of stimulation when applied exogenously - Slows heart and contracts skeletal muscles
4. Be blocked by blocking drugs in a concentration-dependent manner - Blocking receptors causes muscle paralysis
5. Be removed from the synaptic cleft by specific mechanisms - Presence of AChE and choline uptake carrier
46
How many pairs of spinal nerves are there in humans?
31 pairs.
47
Where to motor neuron cell bodies lie?
In the ventral horn of the spinal cord.
48
What is a neuromuscular junction?
A synapse between nerve and muscle.
49
Describe the difference in requirements of fine control and coarse control in terms of neurones.
Fine control = small motor units.
Coarse control = large motor units.
50
Describe Type 1 skeletal muscle.
Slow oxidative (ATP oxidative phosphorylation)
Speed of contraction: slow
Force generated: low
Small motor units
51
Describe Type 2 skeletal muscle.
Fast oxidative (ATP oxidative phosphorylation)
Speed of contraction: intermediate
Force generated: intermediate
Intermediate motor units
Fast glycolytic (ATP through glycolysis)
Speed of contraction: fast
Force generated: high
Large motor units.
52
What kind of mechanism is demonstrated when muscles show fatigue?
Protective/defence mechanism.
53
What can cause a muscle to show fatigue?
Depletion of glycogen
Accumulation of extracellular K+
Accumulation of lactate
Accumulation of ADP + Pi
Central fatigue
54
What is the golgi tendon reflex?
Monitors tension in the muscle
Protects muscle to prevent damage
Tendon reflex less sensitive than stretch reflex
but can override it
55
Describe the two point discrimination of the human body.
Two-point discrimination is a measure of the ability to perceive two distinct points of contact on the skin as separate stimuli. It reflects the density of sensory receptors and the brain's processing capability for different regions of the body.
56
What are the key features of the two point discrimination across the body.
Receptor Density: Regions with a high density of sensory receptors (like the fingertips) have better two-point discrimination compared to areas with fewer receptors (like the back).
Cortical Representation: The size of the somatosensory cortical area dedicated to processing input from a region also affects discrimination. Regions with finer discrimination occupy larger cortical areas.
57
What are the two main divisions of the vertebrate nervous system?
Central Nervous System (CNS) (Brain and Spinal Cord)
Peripheral Nervous System (PNS) (including the Autonomic and Somatic Nervous Systems)
58
What is the key difference between the autonomic and somatic nervous systems?
Autonomic Nervous System (ANS): Involuntary control of smooth muscle, glands, and organs.
Somatic Nervous System (SNS): Voluntary control of skeletal muscles.
59
What are the main functions of the Autonomic Nervous System (ANS)?
Controls smooth muscle contraction and relaxation.
Regulates exocrine and endocrine secretions.
Modulates heartbeat and metabolism.
60
What are the two branches of the Autonomic Nervous System?
Sympathetic Nervous System (SNS) → "Fight or flight" response.
Parasympathetic Nervous System (PNS) → "Rest and digest" response.
61
What neurotransmitters are released by sympathetic neurons?
Preganglionic neurons → Acetylcholine (ACh) (Nicotinic receptors).
Postganglionic neurons → Noradrenaline (NA) (Adrenergic receptors).
Exceptions: Sweat glands and adrenal medulla release ACh instead.
62
What neurotransmitters are released by parasympathetic neurons?
Preganglionic neurons → Acetylcholine (ACh) (Nicotinic receptors).
Postganglionic neurons → Acetylcholine (ACh) (Muscarinic receptors).
63
What are the two types of receptors in the autonomic nervous system?
Nicotinic receptors (Ionotropic, fast response).
Muscarinic & Adrenergic receptors (Metabotropic, G-protein coupled).
64
What are the key effects of the sympathetic nervous system?
Dilates pupils.
Increases heart rate & force.
Decreases digestion & constricts sphincters.
Stimulates glycogenolysis in the liver.
Constricts blood vessels (except in skeletal muscles).
65
What are the key effects of the parasympathetic nervous system?
Constricts pupils.
Decreases heart rate.
Stimulates digestion & relaxes sphincters.
Increases glandular secretions (e.g., saliva, digestive enzymes).
No effect on most blood vessels.
66
How does the ANS control the eye?
Parasympathetic → Constricts pupil (near vision).
Sympathetic → Dilates pupil (far vision, stress response).
67
What are autonomic (visceral) reflexes, and where are they controlled?
Unconscious reflexes regulating homeostasis (e.g., heart rate, blood pressure, digestion).
Controlled by the hypothalamus, brainstem, and spinal cord.
68
What is the baroreceptor reflex, and what does it regulate?
A homeostatic reflex that regulates blood pressure.
Increase in blood pressure → Parasympathetic activation (reduces heart rate).
Decrease in blood pressure → Sympathetic activation (increases heart rate and vasoconstriction).
69
How does the micturition reflex (urination) work?
Parasympathetic activation → Contracts bladder and relaxes sphincter → Urination.
Sympathetic activation → Inhibits bladder contraction → Prevents urination.
70
What is Horner’s Syndrome, and what causes it?
A condition caused by damage to the sympathetic nervous system.
Symptoms include drooping eyelid (ptosis), pupil constriction, and loss of sweating on one side of the face.
71
What are symptoms of autonomic failure?
Dizziness, blackouts, and fatigue due to low blood pressure (postural hypotension).
Can be linked to neurodegenerative diseases affecting the autonomic system.
72
What are the three types of muscle in the human body?
Cardiac muscle (heart muscle, involuntary)
Smooth muscle (internal organs, involuntary)
Skeletal muscle (attached to bones, voluntary)
73
How do cardiac and skeletal muscle differ in structure?
Both have striations and sarcomeres.
Cardiac muscle is electrically coupled via gap junctions and controlled by the autonomic nervous system.
Skeletal muscle is under voluntary control and has multiple nuclei per cell.
74
What is a unique property of smooth muscle?
No striations, arranged in a loose lattice.
Contracts slowly and can maintain tone for long periods.
Innervated by the autonomic nervous system (ANS) and responds to hormones.
75
What are the two main types of muscle contraction?
Isometric contraction: Muscle generates force without changing length (e.g., holding a heavy object).
Isotonic contraction: Muscle changes length while generating force (e.g., lifting weights).
76
How can muscles switch between isometric and isotonic contraction?
A muscle starts as isometric (tension builds) and then becomes isotonic once force overcomes resistance.
77
What gives skeletal muscle its striated appearance?
The alignment of sarcomeres, which are composed of actin and myosin filaments.
78
What is the sliding filament model of muscle contraction?
Actin filaments slide over myosin filaments, shortening the sarcomere.
Requires ATP and calcium ions (Ca²⁺).
79
What are the key factors affecting muscle force production?
Number of active muscle fibers (recruitment).
Frequency of stimulation (summation & tetanus).
Cross-sectional area of the muscle.
Rate of muscle shortening.
Initial muscle length.
80
What are the three main energy sources for muscle contraction?
Phosphocreatine system (lasts ~10 sec, quick ATP source).
Glycolysis (anaerobic, 2 ATP per glucose, produces lactate).
Oxidative phosphorylation (aerobic, ~30-36 ATP per glucose, requires oxygen).
81
What causes muscle fatigue?
ATP depletion.
Accumulation of lactate and H⁺ ions (lower pH).
Calcium ion imbalance in muscle fibers.
82
What are the differences between slow-twitch and fast-twitch muscle fibers?
Slow-twitch (Type I): Uses oxidative phosphorylation, fatigue-resistant, high mitochondria, used for endurance (e.g., posture muscles).
Fast-twitch (Type IIa & IIb):
Type IIa: Oxidative, fatigue-resistant, for moderate-speed movements.
Type IIb: Glycolytic, fatigues quickly, used for sprinting/power movements.
83
Why do fast-twitch (Type IIb) fibers fatigue more quickly than slow-twitch fibers?
They rely on anaerobic metabolism, which produces lactate and fewer ATP molecules.
Have fewer mitochondria and a lower blood supply.
84
How does calcium (Ca²⁺) initiate muscle contraction?
Ca²⁺ is released from the sarcoplasmic reticulum (SR).
Binds to troponin, causing a conformational change.
Exposes myosin-binding sites on actin, allowing contraction.
85
How is muscle contraction terminated?
Ca²⁺ is pumped back into the SR using the SERCA pump (Sarcoplasmic/Endoplasmic Reticulum Ca²⁺-ATPase).
Troponin returns to its original shape, blocking myosin binding sites.
86
How does smooth muscle contraction differ from skeletal muscle contraction?
No T-tubules, contraction is regulated by myosin phosphorylation (not actin exposure).
Slower, longer-lasting contraction.
Controlled by hormones, neurotransmitters (ACh, noradrenaline), and local factors.
87
What is cell signalling?
The process by which cells communicate with each other using chemical and physical signals to regulate growth, development, metabolism, and responses to the environment.
88
Why is cell signalling important?
It controls essential cellular functions like growth, differentiation, metabolism, and responses to stimuli. Defects in signalling pathways can lead to diseases such as cancer, diabetes, and neurological disorders.
89
What are the three main steps of signal transduction?
Signal: Information from outside the cell.
Receptor: A molecule that detects the signal.
Response: Chemical or gene expression changes within the cell.
90
What are the five main types of cell signalling?
Direct contact: Cells communicate by direct membrane interactions.
Gap junctions: Small molecules and ions pass between adjacent cells.
Autocrine signalling: A cell signals itself.
Paracrine signalling: A cell signals nearby cells.
Endocrine signalling: Hormones travel through the bloodstream to distant cells.
91
How do gap junctions function in cell signalling?
Gap junctions allow the direct exchange of ions and small molecules between adjacent cells, enabling coordinated metabolic activity (e.g., electrical synapses in neurons).
92
What is an example of autocrine signalling?
Cancer cells often use autocrine signalling to produce their own growth signals, stimulating uncontrolled proliferation.
93
How does paracrine signalling work at a neuromuscular junction?
The nerve releases acetylcholine, which diffuses across the synaptic cleft to stimulate muscle contraction.
94
What is endocrine signalling, and how does it differ from paracrine signalling?
Endocrine signalling: Hormones are released into the bloodstream and affect distant target cells (e.g., insulin from the pancreas).
Paracrine signalling: The signal acts on nearby cells, not transported through blood.
94
What are ligands, and what are the two types?
Ligands are molecules that bind to receptors to initiate signalling. Types include:
Agonists: Stimulate the receptor (e.g., serotonin).
Antagonists: Inhibit the receptor (e.g., antihistamines).
95
What are the two ways cell-type specificity in signalling is achieved?
Cell-type specific receptor expression: Only certain cells have the necessary receptors (e.g., TRH affects the pituitary but not the liver).
Differential intracellular pathways: Even if receptors are present, only certain cells have the molecular machinery to respond (e.g., adrenaline affects glycogen metabolism in the liver but not in red blood cells).
96
What is ligand-receptor affinity, and why is it important?
Affinity describes how strongly a ligand binds to a receptor. Higher affinity means stronger and longer-lasting signalling.
97
How is affinity mathematically defined in signalling?
The dissociation constant (Kd) represents affinity:
𝐾𝑑=[𝑅][𝐿]/[𝑅𝐿]
Lower Kd = higher affinity (stronger binding).
Higher Kd = lower affinity (weaker binding).
98
How is a small extracellular signal amplified inside a cell?
Enzyme cascades amplify signals: one activated receptor can activate many molecules of the next enzyme, leading to a large response.
99
What is signalling cross-talk, and why is it important?
Cross-talk occurs when signalling pathways share components, allowing integration of multiple signals to produce a unified response.
100
What is signal desensitisation, and why does it occur?
When a receptor is continuously stimulated, its signalling decreases over time. This prevents overactivation and allows the system to reset when the signal disappears.
101
What are receptor enzymes?
Receptor enzymes are cell surface receptors that have intrinsic enzyme activity or are directly linked to enzymes upon activation.
102
What are the five main classes of receptors?
Receptors with intrinsic enzyme activity (e.g., insulin receptor).
Receptors linked to protein kinases.
G-protein-coupled receptors (GPCRs).
Intracellular receptors (e.g., steroid receptors).
Ion channel receptors.
103
What are the four main hormones that regulate blood glucose levels?
Insulin (lowers blood sugar, pancreas).
Glucagon (raises blood sugar, pancreas).
Epinephrine (raises blood sugar, adrenal glands).
Cortisol (raises blood sugar, adrenal glands).
104
What are the two main types of cells in the pancreas involved in insulin and glucagon secretion?
α-cells: Produce glucagon.
β-cells: Produce insulin.
105
What is the structure of the insulin receptor (IR)?
The IR is a transmembrane protein composed of two α-subunits (extracellular) and two β-subunits (cytoplasmic).
106
How is the insulin receptor activated?
Insulin binds to the α-subunits.
This causes a conformational change, bringing the β-subunits together.
Autophosphorylation of the β-subunits activates the receptor.
107
What is the biological significance of insulin receptor activation?
It transduces the signal from the extracellular environment to the intracellular side, initiating cellular responses to insulin.
108
What is the first step in insulin signalling after receptor activation?
Insulin receptor substrate-1 (IRS-1) is phosphorylated, allowing the recruitment of adaptor proteins like Grb2 and Sos.
109
How does Ras activation occur in insulin signalling?
Sos acts as a guanine nucleotide exchange factor (GEF).
It converts inactive GDP-bound Ras into active GTP-bound Ras.
This activates the MAP kinase cascade.
110
How does signal amplification occur in insulin signalling?
Activation of Ras leads to a kinase cascade:
Ras activates Raf kinase.
Raf phosphorylates MEK.
MEK activates MAPK (ERK).
ERK moves to the nucleus and regulates gene expression.
111
How does insulin regulate glucose uptake in cells?
Insulin stimulates the movement of GLUT4 transporters to the plasma membrane in muscle and adipose tissue, increasing glucose uptake.
112
How does insulin stimulate glycogen synthesis?
IRS-1 recruits phosphoinositide 3-kinase (PI-3K).
PI-3K converts PIP2 to PIP3, a second messenger.
PIP3 recruits PDK1, which activates PKB (Akt).
PKB stimulates glycogen synthesis by inhibiting glycogen synthase kinase-3 (GSK-3).
113
What is the difference between Type 1 and Type 2 diabetes?
Type 1 diabetes (T1D): Autoimmune destruction of β-cells, leading to insulin deficiency.
Type 2 diabetes (T2D): Cells become insulin resistant, meaning they do not respond properly to insulin.
114
How does insulin resistance develop in Type 2 diabetes?
Chronic high blood glucose levels lead to desensitization of insulin signalling, reducing GLUT4 movement and glucose uptake.
115
What are two ways to restore insulin sensitivity in Type 2 diabetes?
Dietary control (reducing sugar intake).
Exercise, which increases GLUT4 translocation independent of insulin.
116
What are the main classes of receptors?
The main classes of receptors are:
Receptors with intrinsic enzyme activity
Receptors linked to protein kinases
Receptors coupled to target proteins via a G-protein
Intracellular receptors
Receptors that are ion channels
117
What was the key finding from the clinical trial on caloric restriction and exercise?
The trial showed that severe caloric restriction combined with vigorous exercise led to weight loss, reduced symptoms of Type II diabetes, and a restoration of insulin sensitivity.
118
What is Body Mass Index (BMI), and how is it calculated?
BMI is a measure of body mass based on weight and height. It is calculated as:
BMI = weight (kg)/height (m)
BMI > 30 = Obese
BMI 25–30 = Overweight
BMI < 25 = Normal
119
Why is BMI considered an imperfect measurement?
BMI can be misleading because it does not account for muscle mass, body composition, or variations in height. Tall individuals may appear overweight, short individuals may appear underweight, and athletes may be categorized as obese despite having low body fat.
120
What is the Lipostat Theory of body mass regulation?
The Lipostat Theory (Kennedy, 1953) suggests that body weight is maintained at a ‘set point’ through feedback mechanisms that regulate food intake and energy expenditure.
121
What is leptin, and where is it produced?
Leptin is a hormone produced by adipose (fat) tissue that signals the brain to reduce food intake when fat stores are sufficient.
122
What effect does leptin have on the body?
Leptin suppresses appetite, stimulates the sympathetic nervous system, increases blood pressure, heart rate, and thermogenesis, helping regulate body weight.
123
What happens in leptin-deficient (Lep ob/ Lep ob) mice?
These mice exhibit severe obesity, excessive eating, low body temperature, impaired wound healing, and metabolic disturbances similar to Type II diabetes.
124
What is the role of the leptin receptor (Lepr DB)?
The leptin receptor, located in the hypothalamus, binds leptin and initiates a signalling cascade that reduces food intake and increases energy expenditure.
125
How does leptin activate its signalling pathway?
Leptin binds to its receptor, activating Janus Kinase (JAK), which phosphorylates the receptor. This recruits and activates STAT proteins, which dimerize, enter the nucleus, and promote the production of appetite-suppressing hormones like α-MSH.
126
How does leptin interact with insulin signalling?
Leptin enhances insulin sensitivity in liver and muscle cells, influencing metabolism by modulating IRS-1 and IRS-2 pathways.
127
What is erythropoietin (EPO), and where is it produced?
EPO is a hormone cytokine primarily produced in the kidneys that regulates red blood cell production in response to oxygen levels.
128
How does erythropoietin (EPO) signal within cells?
EPO binds to its receptor (EPO-R), activating the JAK-STAT pathway, leading to transcriptional changes that promote red blood cell production.
129
What is the role of EPO in sports doping?
Synthetic EPO has been used to enhance endurance in athletes by increasing red blood cell count, which improves oxygen delivery to muscles. It has been involved in multiple sports doping scandals.
130
How do the JAK-STAT and Ras-MAPK pathways interact in receptor-linked enzyme signalling?
JAK-STAT primarily regulates gene expression, while the Ras-MAPK pathway controls cell growth and development. These pathways can cross-talk to coordinate metabolic and behavioural responses.
131
What are G protein-coupled receptors (GPCRs), and why are they important?
GPCRs are the largest class of cell-surface receptors, involved in a wide range of physiological responses. About 60% of all drugs target GPCR-mediated pathways.
132
What is the basic structure of a GPCR?
A GPCR consists of:
Extracellular domains (E1–E4)
Seven transmembrane (TM) helices (TM1–TM7) forming a ligand-binding cavity
Cytosolic loops (C1–C3) and a C4 tail (which has a lipid anchor)
133
How do GPCRs interact with ligands?
Small ligands bind within the transmembrane cavity, often covered by loop E2. Larger ligands like proteins and peptides bind to extracellular loops or the N-terminus.
134
What happens when a ligand binds to a GPCR?
Ligand binding causes a conformational change in the transmembrane helices, exposing sites in the cytosolic domain that activate heterotrimeric G-proteins.
135
What are the components of a heterotrimeric G-protein?
A heterotrimeric G-protein consists of:
Gα (binds GDP in the inactive state, GTP in the active state)
Gβ and Gγ (which form a stable dimer)
136
How does a GPCR activate a G-protein?
Ligand binding induces GDP-GTP exchange on Gα, activating it. The G-protein then dissociates into Gα-GTP and a Gβγ dimer, which modulate different cellular targets.
137
How do heterotrimeric G-proteins cycle between active and inactive states?
Gα has intrinsic GTPase activity, slowly hydrolyzing GTP to GDP. This regenerates the inactive Gα-GDP, which re-associates with Gβγ to reset the cycle.
138
How is GPCR signalling regulated?
GPCRs are phosphorylated by GPCR kinases (GRKs), reducing activation. High phosphorylation levels lead to arrestin binding, which stops signalling and promotes receptor internalization.
139
What are the different types of G-proteins and their effects?
G𝑠 : Stimulates adenylate cyclase (e.g., glucagon, epinephrine)
G𝑖 : Inhibits adenylate cyclase (e.g., adenosine, prostaglandin)
G𝑞 : Stimulates phospholipase C (e.g., vasopressin, bombesin)
G𝑡 : Activates cGMP phosphodiesterase (e.g., phototransduction)
G12 : Activates ion channels (e.g., Na+ /H+ exchange)
140
What is the fight-or-flight response, and how is it mediated?
It is an acute stress response triggered by perceived threats. Epinephrine and cortisol are released, increasing heart rate, blood glucose, and muscle energy availability.
141
How does epinephrine signal through GPCRs?
Epinephrine binds β-adrenergic GPCRs, activating G𝑠, which stimulates adenylate cyclase, increasing cAMP levels. cAMP activates protein kinase A (PKA), leading to metabolic and physiological changes.
142
What are the effects of β-adrenergic receptor activation?
Skeletal muscle: Glycogen breakdown (more glucose)
Cardiac muscle: Increased contraction rate
Adipose tissue: Increased lipolysis (fat breakdown)
Pancreas: Glucagon release (raises blood sugar)
143
What is cholera toxin, and how does it affect GPCR signalling?
Vibrio cholerae secretes cholera toxin (CTx), which ADP -ribosylates G𝑠, locking it in an active state. This permanently activates adenylate cyclase, increasing cAMP levels and causing severe diarrhoea.
144
How does cAMP act as a second messenger?
cAMP activates protein kinase A (PKA), which phosphorylates target proteins involved in metabolism, gene expression, and ion transport.
145
How is GPCR signalling terminated?
Gα hydrolyzes GTP to GDP (turning itself off)
Adenylate cyclase acts as a GTPase-activating protein (GAP)
Arrestin binding prevents further activation and promotes receptor recycling or degradation.
146
What are the main types of light receptor cells in the vertebrate eye?
Rod cells detect low light levels and enable night vision, while cone cells detect different wavelengths for colour vision at higher light intensities.
147
What is rhodopsin, and what are its components?
Rhodopsin is a GPCR (G protein-coupled receptor) found in rod cells, consisting of opsin (the protein component) and 11-cis-retinal (a light-absorbing chromophore).
148
How does light activate rhodopsin?
Light absorption causes cis-trans isomerisation of 11-cis-retinal, triggering a conformational change in rhodopsin, which then activates the G-protein transducin (G𝑡).
149
What happens after transducin is activated?
The G𝑡-alpha subunit activates cGMP phosphodiesterase (PDE), which lowers cGMP levels, causing the closure of cGMP-gated ion channels and hyperpolarization of the membrane.
150
How does light affect the membrane potential of rod cells?
In darkness, cGMP keeps ion channels open, maintaining a depolarised state (-40mV). In light, cGMP is degraded, channels close, and the membrane hyperpolarises (-70mV).
151
How does rhodopsin reset after exposure to light?
Guanylate cyclase restores cGMP levels, reopening ion channels. Rhodopsin kinase phosphorylates activated rhodopsin, and arrestin binds to stop activation of transducin.
152
What mechanisms make rod cells less sensitive in bright light?
1. Prolonged cGMP channel closure reduces ion flow.
2. Phosphorylation of opsin reduces transducin activation.
3. Arrestin binding fully inactivates rhodopsin.
153
How long does it take for rods to adapt from bright light to darkness?
20–30 minutes to fully recover sensitivity, reversing high-light adaptation mechanisms.
154
How does colour vision work in humans?
Colour vision relies on three types of cone cells sensitive to different wavelengths:
Blue cones (414–426 nm)
Green cones (530–532 nm)
Red cones (560–563 nm)
155
How do different cone cells detect different wavelengths?
Opsins in cone cells modify the electronic environment around 11-cis-retinal, tuning its sensitivity to specific light wavelengths.
156
How do cephalopods perceive colour despite only having rod-like receptors?
Their U-shaped and W-shaped pupils create chromatic aberration (light diffraction), which their large optic lobes process, allowing them to "see" colour without cone cells.
157
What is colour blindness, and what are its common types?
Colour blindness occurs due to mutations in opsin genes, leading to missing or malfunctioning cones:
Protanopia: Missing red (L-cone).
Deuteranopia: Missing green (M-cone).
Tritanopia: Missing blue (S-cone).
158
How was John Dalton’s colour blindness scientifically confirmed?
In 1995, DNA sequencing of Dalton’s preserved eyes showed a deletion in the green (M-cone) opsin gene, confirming he was a genetic dichromat (deuteranope).
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Why might colour blindness persist in human populations?
Dichromats detect camouflaged objects better than trichromats, which may have given evolutionary advantages in activities like hunting and warfare.
160
Why does sildenafil (Viagra) cause blue-tinged vision?
Sildenafil inhibits PDE-5, but also affects PDE-6, which regulates blue-green colour discrimination, leading to temporary blue vision in some users.
161
What are intracellular receptors, and how do they differ from other receptors?
Intracellular receptors are located inside the cell, typically in the cytoplasm or nucleus. They bind small, lipid-soluble ligands that can diffuse across the plasma membrane, unlike membrane-bound receptors.
162
How does nitric oxide (NO) function as a signalling molecule?
NO diffuses across cell membranes and activates soluble guanylate cyclase (GC), which converts GTP into cGMP, a second messenger that alters target protein activity.
163
What is the historical significance of nitric oxide in medicine?
Nitroglycerine (NG) was discovered in 1846 and later used for angina relief. In 1977, Ferid Murad discovered that NO is released from NG, and in 1987, Louis Ignarro identified NO as endothelium-derived relaxing factor (EDRF).
164
How does nitric oxide help regulate blood pressure?
NO is released by endothelial cells in response to high blood pressure, activating guanylate cyclase in smooth muscle cells, leading to vasodilation and reduced blood pressure.
165
How does NO synthesis occur in blood vessels?
Increased Ca²⁺ levels activate nitric oxide synthase (NOS), which converts L-arginine into L-citrulline and NO. The NO then diffuses into smooth muscle to stimulate guanylate cyclase.
166
What are the three main isoforms of nitric oxide synthase (NOS) and their functions?
nNOS (NOS1): Nervous system development, peristalsis, sexual arousal
iNOS (NOS2): Immune defense, macrophage activation
eNOS (NOS3): Vascular tone regulation, angiogenesis, insulin secretion.
167
What is the role of cGMP in nitric oxide signalling?
cGMP activates protein kinase G (PKG), which phosphorylates myosin light chains in smooth muscle, leading to relaxation and blood vessel dilation.
168
How does sildenafil (Viagra) enhance NO signalling?
Sildenafil is a PDE-5 inhibitor, preventing the breakdown of cGMP, prolonging smooth muscle relaxation and increasing blood flow.
169
What are the side effects of sildenafil, and why do they occur?
Low blood pressure and headaches (PDE-5 is in vascular smooth muscle)
Increased heart rate (tachycardia) (PDE-3 inhibition)
Blue-tinged vision (PDE-6 inhibition affects colour discrimination in the retina)
170
What are oestrogens, and how are they synthesised?
Oestrogens are steroid hormones derived from androgens via the enzyme aromatase. The four main types are:
E1 (Oestrone): Predominant in menopause
E2 (Oestradiol): Dominant during reproductive years
E3 (Oestriol): Found in pregnancy
E4 (Oestetrol): Also produced during pregnancy
171
How does the oestrogen receptor (ER) function as a transcription factor?
Oestrogen binds ER in the cytoplasm, releasing it from Hsp90 (a chaperone protein).
The ER-oestrogen complex enters the nucleus, dimerises, and binds to oestrogen response elements (EREs).
ERE binding initiates gene transcription.
172
How does steroid hormone signalling differ from other pathways?
Steroid hormones directly regulate gene transcription without second messengers or signal amplification, making the receptor itself both a sensor and an effector.
173
What is tamoxifen, and how does it affect oestrogen signalling?
Tamoxifen is a non-steroidal ER antagonist used to treat ER-positive breast cancer. It prevents ER activation by stabilising an inactive receptor conformation.
174
Why are some breast cancers resistant to tamoxifen?
The G-protein-coupled oestrogen receptor (GPER) can activate oestrogen-responsive pathways independently of ER, making tamoxifen ineffective in some cases.
175
How does oestrogen regulate multiple physiological processes?
Different isoforms and dimers of ER (ERα, ERβ, and heterodimers) allow oestrogen to regulate reproduction, cardiovascular function, immunity, brain development, and bone growth.
