Cellular neuroscience and physiology Flashcards
1
Q
Give the components of the Nernst equation
A
E ion: Equilibrium potential for the ion (in millivolts, mV)
R: Universal gas constant (8.314 J/mol·K)
T: Absolute temperature (in Kelvin; 37°C = 310 K)
z: Valence (charge) of the ion (e.g., +1 for K⁺ or Na⁺, -1 for Cl⁻)
F: Faraday’s constant (96,485 C/mol)
[ion] outside: Extracellular concentration of the ion
[ion] inside: Intracellular concentration of the ion
2
Q
What do all the components of the GHK equation mean?
A
Vm: Membrane potential (in volts or millivolts)
R: Gas constant (8.314 J/mol·K)
T: Temperature in Kelvin (310 K at body temp)
F: Faraday’s constant (96,485 C/mol)
Pion: Membrane permeability for that ion
[ion] out [ion] in: Extracellular and intracellular concentrations
3
Q
At what speed do thick, myelinated axons typically conduct action potentials?
A
40–65 m/s
4
Q
What initiates excitation-contraction coupling in muscles?
A
Action potential (AP) propagation into T-tubules
5
Q
What receptors are involved in excitation-contraction coupling?
A
Dihydropyridine receptors (DHPR) and ryanodine receptors (RyR)
6
Q
What happens when calcium is released from the sarcoplasmic reticulum?
A
Calcium binds to troponin, which causes tropomyosin to shift, exposing binding sites on actin
7
Q
What proteins are involved in the sliding filament mechanism?
A
Actin (thin filaments) and myosin (thick filaments)
8
Q
At a molecular level, how do muscles contract and relax?
A
Myosin binds to actin and performs a power stroke; ATP then detaches myosin from actin to reset the cycle
9
Q
What triggers detachment of myosin from actin?
A
ATP binding to myosin
10
Q
What causes the power stroke?
A
Breakdown of ATP into ADP and Pi, changing the angle of the myosin head
11
Q
What is rigor mortis and why does it occur?
A
Rigor mortis is the post-mortem stiffening of muscles due to ATP depletion, preventing detachment of actin-myosin cross-bridges
12
Q
How is calcium removed to end contraction?
A
Calcium is actively pumped back into the SR using ATP
13
Q
Outline the sequence that occurs from action potential to muscle contraction and relaxation
A
AP → Depolarization → DHPR/RyR activation → Ca²⁺ release → Contraction → Ca²⁺ reuptake by SR
14
Q
What does the length-tension curve show?
A
Optimal muscle tension occurs at an ideal sarcomere length where actin-myosin overlap is optimal
15
Q
What is a myogram?
A
A graph that records twitch tension in muscle
16
Q
How are skeletal muscles classified?
A
Based on twitch speed and appearance:
Type 1 (Slow-twitch, red, high myoglobin)
Type 2A
Type 2B (Fast-twitch, white, low myoglobin)
17
Q
What is tetanus in muscle physiology?
A
A sustained contraction caused by rapid, repeated stimuli
18
Q
What is the tetanic fusion frequency?
A
The frequency of APs needed to produce a smooth contraction without visible twitches
19
Q
In 10 points, describe the mechanism of excitation contraction coupling in skeletal muscle
A
- Influx of Ca2+ into presynaptic terminal (and fusion of vesicles).
- Release of neurotransmitter acetylcholine (ACh).
- Binding of ACh to (nictotinic) ACh receptor (AChR).
- Influx of Na+ (at motor end plate).
- Propagation of AP.
- Activation of dihydropyridine receptor (DHPR) (T-tubules;
conformational coupling with ryanodine receptors (RyR)). - Release of calcium from sarcoplasmic reticulum (SR) (calcium-induced
calcium release (CICR)). - Binding of Ca2+ to troponin (conformational change tropomyosin).
- Cross Bridge formation (Actin and Myosin; ATP).
- Cross bridge cycling (Power Stroke; release of ADP + Pi)
20
Q
What are intercalated discs?
A
Specialized structures containing:
Fascia adherens and desmosomes (mechanical junctions)
Gap junctions (electrical connections between adjacent cells)
21
Q
Why are gap junctions important in cardiac muscle?
A
They allow electrical impulses to rapidly propagate across cells, enabling synchronized contraction
22
Q
What are the 2 types of cardiac action potentials?
A
Slow response (Pacemaker cells - SAN, AVN)
Fast response (Atrial/ventricular myocytes, Purkinje fibers)
23
Q
Where is the action potential initiated in cardiac muscle?
A
The sinoatrial node
24
Q
Which cells show fast response action potentials?
A
Atrial and ventricular myocytes, Purkinje fibers
25
How do pacemaker cells generate APs without neuronal input?
Due to unstable RMP and funny channels (If) that allow Na⁺ influx at hyperpolarized potentials
26
Describe the 5 phases of fast response action potentials
Phase 0: Rapid depolarization (Na⁺ influx)
Phase 1: Initial repolarization (K⁺ efflux)
Phase 2: Plateau phase (Ca²⁺ influx via L-type channels and NCX)
Phase 3: Repolarization (K⁺ efflux continues)
Phase 4: Resting membrane potential
27
What is the main difference in EC coupling between skeletal and cardiac muscle?
In cardiac muscle, DHPR and RyR are not physically coupled. Calcium entry through DHPR (L-type channels) triggers calcium release from SR via calcium-induced calcium release (CICR)
28
How is cardiac relaxation achieved?
Ca²⁺ removed by SERCA and NCX
Tropomyosin blocks actin binding sites as Ca²⁺ unbinds from troponin
29
What is the cardiac absolute refractory period?
It’s the period during which a second AP cannot be triggered. It prevents tetany and allows full relaxation between beats
30
What is the Frank-Starling law?
The heart pumps all the blood it receives: increased stretch → increased contractile force
31
What is positive chronotropy?
Increased heart rate
32
What is positive inotropy?
Increased contraction strength
33
What is positive lusitropy?
Increased relaxation rate
34
What neurotransmitters are involved in sympathetic stimulation?
Adrenaline and noradrenaline
35
What structural proteins are found in cardiac muscle?
Actin & myosin (filaments)
Titin (elasticity/stretch sensor)
C-protein, α-actinin, nebulin (scaffolding proteins)
36
Why does cardiac muscle appear striated?
Due to alternating A (dark) and I (light) bands — same as skeletal muscle
37
Why would fibrillation occur?
If the absolute refractory period is decreased
38
What is RyR?
Ryanodine receptors
39
What is the NCX?
Sodium-calcium exchanger) 3Na+-1Ca2+
Found in the sarcolemma of cardiac myocytes
Removes cytosolic calcium from cardiac muscles during diastole
40
Which has a higher resistance to stretch, cardiac or skeletal muscle?
Cardiac
40
What is diastole?
Relaxation
41
How does NCX work?
During repolarization, intracellular Ca²⁺ must be lowered.
NCX uses the inward Na⁺ gradient (more Na⁺ outside the cell) to export Ca²⁺ against its concentration gradient
42
Describe the morphology of a smooth muscle cell
Spindle-shaped, 100–300 μm long, 2–5 μm wide
Single nucleus
No striations
Embedded in connective tissue matrix, arranged in series/parallel
43
What kind of muscle is non-striated?
Smooth
44
What nervous system controls smooth muscle?
Autonomic Nervous System (ANS):
Sympathetic and parasympathetic branches
Can be excitatory (contract) or inhibitory (relax)
Involuntary control
45
What is the difference between single unit and multi unit smooth muscle?
Single-unit: Connected by gap junctions → contract as one (e.g., intestines, uterus)
Multi-unit: Each cell contracts independently (e.g., iris, arrector pili)
46
Define phasic contractions
Quick, transient contractions (e.g., peristalsis)
47
Define tonic contractions
Sustained contractions, resist fatigue (e.g., blood vessel tone)
48
What is pharmacomechanical coupling?
Contraction regulation without changes in membrane potential, using hormones or drugs
49
Where does the calcium for contractions come from in smooth muscles?
Extracellular space (main source)
Sarcoplasmic reticulum (SR) (less developed than in other muscles)
SR adjacent to caveolae (membrane invaginations)
50
What surrounds myofibrils?
Sarcoplasmic reticulum
51
Is smooth muscle contraction thin or thick filament regulated?
Thick filament regulated (myosin-based)
52
Describe the 5 step contraction mechanism in smooth muscle
Ca²⁺ enters and binds calmodulin
Ca²⁺-calmodulin activates myosin light chain kinase (MLCK)
MLCK phosphorylates myosin heads → enables binding to actin
Myosin ATPase activity enables cross-bridge cycling
Myosin phosphatase dephosphorylates myosin → relaxation
53
What are varicosities?
Pre-synaptic terminals
54
How does smooth muscle contraction differ from skeletal and cardiac?
Calmodulin binds to calcium, which then activates MLCK to phosphorylate the myosin heads and induce cross bridge cycling.
In skeletal muscle, this is achieved by calcium binding to troponin, which allows the myosin heads to bind.
55
What is the latch state in smooth muscle?
A state of sustained contraction with low ATP use
Occurs when some myosin-actin cross-bridges are dephosphorylated but remain attached
Cross-bridge detachment rate slows → maintains tone
56
Why is the smooth muscle latch state important?
It allows long-lasting contractions (e.g., blood vessel tone) with minimal energy consumption
57
What is the only kind of muscle that is thick filament regulated?
Smooth
58
Give 3 examples of multi unit smooth muscle
Iris
Vasculature
Airways
59
Give 2 examples of single unit smooth muscle
GI tract
Bladder
60
What is the unit of ion channel conductance?
Picosiemens (pS) – most channels range from 0.1–100 pS
61
What are ionotropic receptors? Give one example
Fast-acting receptors that form ion channels. Example: nAChR (nicotinic acetylcholine receptor)
62
What are metabotropic receptors? Give one example
Slower receptors that activate intracellular signaling pathways (GPCRs). Example: mAChR, adrenergic receptors
63
How does water move across membranes?
Through aquaporins (AQPs) – protein water channels
64
What are the 3 major types of solute carriers?
Uniporters – transport one substance (e.g., GLUT2 for glucose)
Symporters – move ≥2 substances in same direction (e.g., NKCC2 in kidney)
Antiporters – move substances in opposite directions (e.g., Na⁺/H⁺ exchanger)
65
What is secondary active transport?
Uses energy from an existing gradient to move other substances against theirs.
Example: 3Na⁺/Ca²⁺ exchanger (NCX) – antiporter using Na⁺ gradient to remove Ca²⁺
66
What is primary active transport?
Transport directly coupled to ATP hydrolysis
67
How does the sodium potassium pump work?
3 Na⁺ out, 2 K⁺ in, 1 ATP hydrolyzed
Maintains resting membrane potential
α subunit binds ATP, Na⁺, K⁺, ouabain (inhibitor)
68
Give an example of an ABC transporter
CFTR (cystic fibrosis transmembrane regulator) – chloride channel affected in CF
69
What causes cystic fibrosis?
Mutations in CFTR gene → defective Cl⁻ transport → thick mucus buildup in lungs, pancreas, etc
70
What removes calcium during cardiac relaxation?
SERCA, NCX, and Ca²⁺ ATPases
71
What is an ABC transporter?
ATP-Binding Cassette transporter
They are a superfamily of membrane proteins that actively transport a variety of substances across cellular membranes using ATP hydrolysis.
72
What is osmotic pressure?
The pulling force that draws water into a solution due to non-penetrating solutes
73
What is hydrostatic pressure?
The pushing force exerted by a stationary fluid on a boundary or object (e.g., the capillary wall)
74
What happens when hydrostatic and osmotic pressure are equal?
Net water movement stops; equilibrium is reached
75
Define molarity
The number of moles of solute per litre of solution (mol/L)
76
Define osmolarity
The number of particles (osmoles) per litre of solution (Osm/L)
77
Give an example where molarity = osmolarity
Glucose: it does not dissociate, so 5.5 mM = 5.5 mOsm
78
Give an example where osmolarity is larger than molarity
NaCl dissociates into Na⁺ and Cl⁻, so 1 M NaCl = 2 Osm
79
What's the difference between molarity and osmolarity?
Molarity counts molecules
Osmolarity counts particles those molecules form in solution
80
Define osmolality
Osmoles per kilogram of solvent (Osm/kg) – more precise for clinical/human physiology
81
What is the normal plasma osmolality?
~280–295 mOsm/kg
82
What is tonicity?
The effect of osmotic pressure on cell volume; it tells us whether cells will shrink, swell, or stay the same
83
What is an isotonic solution?
Has the same osmolarity as the cell’s cytoplasm → no net water movement
84
What happens to a cell in a hypotonic solution?
Water enters the cell → it swells and may burst
85
What happens to a cell in a hypertonic solution?
Water leaves the cell → it shrinks (crenates)
86
What are RVD and RVI?
RVD (Regulatory Volume Decrease): response to swelling (cell loses solutes & water)
RVI (Regulatory Volume Increase): response to shrinkage (cell gains solutes & water)
87
A red blood cell is placed in 600 mOsm/L NaCl + glucose. What happens?
It’s in a hypertonic solution → water leaves → cell shrinks
88
What are the divisions of the nervous system?
Central nervous system (CNS): brain and spinal cord
Peripheral nervous system (PNS):
Somatic (voluntary) – e.g., motor neurons to skeletal muscles
Autonomic (involuntary) – e.g., to heart, GI tract
Subdivided into:
Parasympathetic ("rest & digest")
Sympathetic ("fight or flight")
89
What is the synaptic delay
~0.5 milliseconds due to vesicle fusion and neurotransmitter diffusion
90
What 3 proteins assist with vesicle fusion?
Fusion protein macromolecules (FPMs) help with vesicle docking
Clathrin: coats vesicles for endocytosis
Dynamin: pinches the vesicle off for recycling
91
What are the 3 main mechanisms of neurotransmitter removal?
Enzymatic breakdown (e.g., acetylcholinesterase)
Reuptake into presynaptic terminal
Uptake into nearby glial cells
92
What is an EPSP?
Excitatory postsynaptic potential – a small depolarization caused by Na⁺ influx, brings the neuron closer to firing
93
What 2 neurotransmitters cause EPSPs?
Glutamate
Acetylcholine (at nicotinic receptors)
94
What is an IPSP?
Inhibitory postsynaptic potential – a small hyperpolarization, making the neuron less likely to fire
95
What ions and transmitters are involved in IPSPs?
Cl⁻ influx (via GABA, glycine)
K⁺ efflux may also contribute to hyperpolarization
96
Are EPSPs and IPSPs all or nothing?
No, they are graded potentials, unlike action potentials which are all-or-none
97
What is spatial summation?
Multiple inputs from different synapses sum at the axon hillock
98
What is temporal summation?
Repeated input from the same synapse over time sums to trigger an AP
99
What is convergence in synaptic physiology?
Many presynaptic neurons synapse onto one postsynaptic neuron → integration of signals
100
What is divergence in synaptic physiology?
One presynaptic neuron synapses onto many postsynaptic neurons → signal amplification/distribution
101
What is presynaptic inhibition?
A third neuron inhibits neurotransmitter release from the presynaptic neuron (e.g., neuron B inhibits neuron A, which excites neuron C)
102
Why is presynaptic inhibition physiologically useful?
It allows precise regulation of neurotransmitter release and signal strength
103
What is the difference between a neurone, a nerve fibre, and a nerve?
Neuron: A single nerve cell
Nerve fibre: The axon of a neuron
Nerve: A bundle of nerve fibres
104
What is an intracellular recording?
A technique where one electrode is placed inside a cell and one outside to record electrical activity of a single neuron
105
What is an extracellular recording?
A technique where both electrodes are outside the cells and record from populations of neurons
106
What property of membranes allows voltage to be stored across them?
Capacitance — the lipid bilayer can store charge and separate it across the membrane
107
What is the formula for voltage in relation to capacitance?
Voltage=
Capacitance/Charge stored
108
What is saltatory conduction?
APs leap from one node of Ranvier to the next, increasing speed of propagation in myelinated axons
109
Why do finer fibres conduct more slowly?
They have higher internal resistance and are usually unmyelinated
110
What is the effect of demyelination on AP conduction?
Slower conduction velocity
May lead to conduction block
Long-term = axon death
111
What is Guillain-Barre syndrome?
An acute PNS demyelinating disorder often triggered by infection
Symptoms: limb weakness, tingling, poor coordination
112
What is multiple sclerosis?
A CNS demyelinating disorder linked to autoimmunity, genetics, and viral triggers
Symptoms: numbness, weakness, mobility issues
113
What is a compound action potential?
The sum of action potentials from a population of neurons recorded via extracellular electrodes
114
How is a compound AP different from a single neuron AP?
Single AP: all-or-none
Compound AP: graded based on the number of fibres recruited
115
What determines the size of a compound action potential?
Stimulus strength
116
What is TTX and how does it affect neurons?
Found in pufferfish
Potent Na⁺ channel blocker
Binds extracellularly, prevents APs → respiratory paralysis
117
What does TEA+ block?
K⁺ channels, preventing repolarization and prolonging action potentials
118
What is Novichok and how does it affect neural transmission?
Acetylcholinesterase inhibitor
Prevents breakdown of ACh
Causes continuous muscle stimulation, spasms, and asphyxiation
119
What allows saltatory conduction to be so fast?
Myelin insulation + concentration of Na⁺ channels at nodes of Ranvier
120
What happens if sodium or potassium channels are blocked?
Na⁺ blocked (e.g. TTX): No AP initiation
K⁺ blocked (e.g. TEA⁺): Slowed repolarization
