Homeostasis + Membrane Transport Flashcards

1
Q

Define Homeostasis and why it is important?

A

The ability of the body to maintain a relatively stable internal environment. This is important so that cells can function properly.

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2
Q

What are the control systems for homeostasis?

A

Nervous system (acts quickly) and the endocrine system- hormones (acts slower). Act together or separately. Negative feedback control systems to maintain homeostasis.

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3
Q

What’s an example of positive feedback control?

A

Birth: oxytocin induce contractions and labour more and more until the women has given birth.

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4
Q

How is the 42 L of our total body water (TBW) divided up?

A

3 L plasma (fluid components of blood) and 11 L interstitial fluid -both a part of the ECF. 28 L intracellular fluid -ICF distinct.

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5
Q

State whether the following have a higher concentration on the inside or outside of the cell:
Sodium ions, Potassium ions, Calcium ions, Chloride ions, and Proteins.

A

Sodium ions: outside. Potassium ions: inside. Calcium ions: outside. Chloride ions: outside. Proteins: inside.
SALTY BANANA DIPPED IN CHOCOLATE.

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6
Q

How are ion concentration maintained by the plasma membrane?

A

Provides physical separation, regulates exchange of substances, and communicates with its environment.

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7
Q

What are the functions of membrane proteins? (5)

A

Receptors for hormones, neurotransmitters and ligands, enzymes, transporters, cell recognition (antigens) and cytoskeleton anchors (shape).

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8
Q

Membrane transport mechanisms (5)

A

1.endocytosis/ exocytosis
2. simple diffusion
3. diffusion
4. facilitated diffusion/ transport
5. active transport.

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9
Q

What is simple diffusion?

A

The movement of molecules due to their random thermal motion. Molecules move from areas of high concentration to low concentration (down gradient) until chemical (dynamic) equilibrium is reached. Lipid soluble substances can move through the membrane without help.

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10
Q

What is Fick’s First Law? Describe the variable we’re calculating for, and the variables in the equation.

A

Fick’s First Law of Diffusion can be used to predict simple diffusion. Fick’s first law calculates for J = net rate of diffusion in moles or grams per unit time. Using k = boltzmann constant, T = absolute temp, r = molecular radius, and n = viscosity of the medium, A = total surface area of the membrane for diffusion, and dc/dx = concentration gradient of the solute.

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11
Q

What is diffusion?

A

Polar molecules (ions + water-soluble molecules) cannot diffuse directly through the cell membrane due to the hydrophobic fatty acid region. They require a protein channel/ pore - this is diffusion. The driving force is the concentration gradient still. e.g. water moves through membranes through channels called aquaporins.

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12
Q

What are the factors which affect the rate of diffusion through protein channels? (5) - Can also call this factors affecting the rate of movement through protein leak channel

A

-Size of the molecule
-Charge of the molecule and channel
-Electrochemical gradient
-Pressure gradient
-Hydration energy (“Hille’s theory of closest fit” - water shell must be removed by the channel without the ion “knowing it” so ion remains “energetically stable”- water re-added on other side)

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13
Q

Describe how these factors affect the rate of diffusion / rate of movement through protein leak channels.

A

Some of these factors act as filters preventing one ion from passing through another ion’s channel, others act as chemical specificity.
-Filters: size, charge and hydration energy
-Chemical specificity: electrochemical, and pressure gradients

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14
Q

Describe permeability

A

A measure of how easily an ion can cross a membrane (through pores/ leak channels). -Depends upon the number and type of protein channel in the membrane

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15
Q

A typical cell at rest has the following ion permeabilities:
Na+
K+
Cl-
Which is the most and least permeable?

A

PNa+ = 2 x 10^-8 cm/sec (least permeable)
PK+ = 2 x 10^-6 cm/sec
PCl- = 4 x 10^-6 cm/sec (most permeable)

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16
Q

What is facilitated diffusion?

A

This is a form of carrier mediated transport (shape change allows the molecules to cross). Driving force is still concentration gradient. e.g. glucose uniporter - really large molecules.
Characteristics include - chemical specificity, competitively inhibited, and saturation kinetics.

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17
Q

What is active transport?

A

A form of carrier mediated transport. Moves substances against its concentration gradient. Requires energy (ATP)
e.g. Na+ / K+ ATPase pump
Characteristics include - chemical specificity, competitively inhibited, and saturation kinetics.

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18
Q

What are the functions of the Na+ / K+ pump?

A

Helps maintain the concentration gradients for Na+ and K+ across the cell membrane. Causes slight increased negativity inside the cell (more positive charge is being removed than replaced). Keeps the cells from swelling and bursting due to osmosis.

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19
Q

What are the inhibitors of the Na+ / K + pump?

A

Metabolic inhibitors can block the Na+ / K + pump
-Ouabain (from poison arrow tree), die of cardiac arrest
-Digoxin (from foxglove plant), drug for heart failure.
Inhibits the pump by binding to the ion pathway - when the pump is open to the extracellular environment, prevents K + binding.
- These are specific drugs for the isoform of the Na+ / K+ pump. Alpha 2 subtype is in our heart, and Ouabain + digoxin bind more to this subtype.

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20
Q

What is the meaning of electrogenic, what scenario is the term used in?

A

3 positive charges move out of the cell while only 2 positive charges move in. This is the case with the sodium / potassium channel - 3 sodiums out, 2 potassium in.

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21
Q

Define osmosis

A

Water movement / diffusion. Water moves down its concentration gradient due to its thermal motion. High solute concentration = low water concentration, low solute concentration = high water concentration - water concentration is determined by the number of solute particles in solution (not on their size). Water moves from low solute to high solute - this net movement of water down concentration gradient is called osmosis.

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22
Q

Define osmol

A

Unit to describe the # of solute particles in solution that cause osmosis.

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23
Q

Define osmolality

A

of osmol/Kg of water.

Body fluids (ICF, ECF) are normally 300 mOsmol/ Kg

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24
Q

Define osmolarity

A

of osmol/ L of water

*osmolality and osmolarity can be considered the same thing in this course

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25
Q

Define tonicity

A

Ability of a solution to cause osmosis across a cell.

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26
Q

Describe Isotonic solution

A

No net movement of water. Outside of cell has same osmolarity as inside.

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27
Q

Describe Hypertonic solution

A

Higher solute outside cell than inside. Water moves out of cell, causes cell to shrivel.

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28
Q

Describe Hypotonic solution

A

Higher solute inside than outside the cell. Water moves into cell, causes cell to swell.

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29
Q

What are osmo receptors?

A

Neurons that indicate whether solution is isotonic, hypertonic or hypotonic.

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30
Q

Describe Cystic Fibrosis

A

Genetic disorder that affects the lungs (+other organs) - Caused by mutation which leads to abnormal protein called CF transmembrane conductance regulator. Part of a special chloride transporter that regulates the compponents of mucus lining the lungs. Without CFTR function, the periciliary liquid becomes more viscous and sticks to cilia and they therefore can’t beat the mucus and debris out of lungs, can get infection easily.

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31
Q

Describe the Darrow-Yannet Diagram

A

A way to look at relative changes in the volume and concentration of the ICF and ECF compartments. Helps determine the net movement of water across the cell membrane.
Looks at: water load, water loss, solute load and solute loss. Changes always occur to the ECF first, and then the ICF responds.

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32
Q

Describe water load

A
  1. Volume of ECF increases and osmolarity decreases
  2. Water moves into ICF by osmosis (until osmolarity equals out)
  3. Volume of both ECF and ICF is greater than normal, osmolarity is lower in both.
33
Q

Describe water loss

A
  1. Volume of ECF decreases and osmolarity increases
  2. Water moves into the ECF by osmosis until osmolarity equals
  3. Volume of both ECF and ICF is lower than normal, osmolarity is higher in both.
34
Q

Describe solute load (high salt diet or drinking sea water)

A
  1. Osmolarity of ECF increases (if salt water then volume increases too)
  2. Water moves out of ICF into ECF by osmosis until osmolarity equals
  3. Osmolarity of both ECF and ICF is greater than normal, ECF is greater volume, ICF is smaller volume.
35
Q

Describe fluid balance - solute loss

A
  1. ECF osmolarity decreases
  2. Water moves into ICF by osmosis until osmolarity equals
  3. Volume of ECF lower than normal, volume of ICF greater than normal, osmolarity of both is lower than normal.
36
Q

Describe the site of exchange between plasma and interstitial fluid

A

The capillary endothelium can have gaps between cells (8 nm opening). Most dissolved substances are 0.3-1.2 nm in diameter so they pass through easily by bulk flow, but most proteins are too large.

37
Q

What are the 4 forces that act on the fluid exchange between the plasma and interstitial fluid? What are these known as?

A

2 hydrostatic pressures (fluid):
- Capillary hydrostatic pressure of the plasma (Pc)
- Interstitial fluid hydrostatic pressure (Pif)
2 colloid osmotic pressures (oncotic):
- Plasma colloid osmotic (oncotic) pressure
- Interstitial colloid osmotic (oncotic) pressure
*these are known as starling’s forces

38
Q

Describe Capillary hydrostatic pressure of the plasma (Pc)

A

Pressure from the blood (plasma) in the capillary. Usually higher at arteriole end (25 mmHg) than veinous end (10 mmHg). Reduction in pressure as blood flows through.

39
Q

Define Starling’s forces

A

Factors that influence the fluid exchange at endothelium, between plasma and interstitial fluid

40
Q

Describe Interstitial fluid hydrostatic pressure (Pif)

A

Pressure on the fluid in the interstitial spaces, varies from organ to organ (-6 to +6 mmHg). Causes filtration when negative, or reabsorption when positive. Pif is negative in subcutaneous tissue, and positive in encapsulated organs.

41
Q

Describe Plasma colloid osmotic (oncotic) pressure (πp)

A

Pressure caused by osmosis due to proteins in the plasma. Pressure = 28 mmHg. Causes reabsorption.

42
Q

Describe Interstitial colloid osmotic (oncotic) pressure (πif)

A

Pressure caused by osmosis due to proteins in the interstitial space. Pressure = 5 mmHg (fewer proteins), causes filtration.

43
Q

Define osmotic pressure

A

Tendency of a solution to cause osmosis. Water will move with a particular pressure = osmotic pressure. It depends on the number of solute particles in solution, in this case proteins for example.

44
Q

What is Starling-Landis Equation?

A

NFM = Kf [( Pc - Pif) - (πp - πif)]
NFM: net fluid movement
Kf: filtration coefficient. Can assume it equals 1 unless otherwise stated.

45
Q

Describe the filtration coefficient (Kf)

A

Represents the permeability of the capillary and surface area of the endothelium. Varies in different tissue (e.g. very high in kidney - very leaky, compared to muscle - less leaky). Constant in any single capillary bed (under normal conditions). Assume it equals 1 unless otherwise stated.

46
Q

Define Oedema (edema?)

A

Build-up of fluid in the interstitial fluid. The swelling of tissue due to the increase in interstitial fluid (30% increase to feel + look swollen)

47
Q

Describe the lymphatic system

A

A series of small channels leading to larger and larger vessels. Contain distinct fluid solution called lymph fluid which contains other components beyond interstitial fluid. Found in skin, GI genitourinary and respiratory systems. Part of the immune system. Drains the tissue of excess interstitial fluid.
Endothelial cells act as one way doors - once fluid is in lymphatic system it can’t exit the same way, but eventually it does end up back in our blood.

48
Q

How is the fluid moved along in the lymphatic system?

A
  • Pressure gradient (respiratory system - breathing changes causes pressure)
  • Smooth muscle pumps and valves
  • Contraction of skeletal muscle (skeletal muscle pump)
    *Gaps for bigger particulates e.g. proteins
49
Q

What are the 4 different ways that Oedema can occur?

A
  1. Decreased plasma proteins
  2. Partial blockage of venous return to the heart
  3. Blockage of the lymphatic system
  4. Tissue damage
50
Q

Describe how decreased plasma proteins can cause oedema and give an example of how this could happen

A

Decrease in plasma colloid osmotic pressure (oncotic), e.g. Kwashiorker (malnutrition) - seen in severely malnourished children, particularly those with low protein diets. Symptoms include a severely blotted belly and swelling in the hands and feet. Lack of dietary protein affects the fluid balance because it decreases the oncotic pressure of the plasma (causes increased filtration).

51
Q

Describe how partial blockage of venous return to heart can cause oedema and give an example of how this could happen

A

Blood flow is reduced, pressure in plasma builds up (blood volume increases), increases capillary hydrostatic pressure of the plasma - increases net fluid movement (more interstitial fluid). e.g. plaque build-up.

52
Q

Describe how blockage of the lymphatic system can cause oedema and give an example of how this could happen

A

Results in oedema because interstitial fluid can’t enter lymphatic system (no lymph fluid movement), so volume of IF increases. e.g. elephantiasis - caused by parasitic worm that resides in the lymphatic vessels. The worms will damage and cause blockage of the lymphatic vessels.

53
Q

Describe how tissue damage can cause oedema

A

More permeable than usual - changes Kf (filtration coefficient), damage causes increased permeability. e.g. histamine, thermal damage, cytokines, and mechanical damage are all causes of tissue damage. Allergies caused by histamine compound used for generalized inflammation (increases permeability of capillaries) part of inflammatory response - fluid transfer from blood to interstitial fluid. Anaphylaxis causes release of histamine all over.

54
Q

Describe the resting membrane potential

A

Electric potential across the membrane - the inside of our cells are negative with respect to the outside of the cell - approximately -70mV, can vary slightly. Generated by the selective permeability of the membrane to particular ions (through channels + protein carriers)

55
Q

What is the resting membrane potential affected by?

A
  • Permeability of membrane to various ions
  • Concentration gradients of the ions
    K+ : wants to leave + can leave (very permeable + high concentration gradient) - contributes the most to the electrical gradient
    Na+ : wants to enter cell + can but not as permeable (has less channels), concentration gradient also not as strong
    Cl- : concentration gradients means it wants to enter cell but electrical gradients means it does not (negative inside cell)
    Ca 2+ : doesn’t really contribute to electrical gradient
56
Q

What is the equilibrium potential (Ex)?

A

The electrical potential required to offset the force of the concentration gradient of the ion.
There are two forces that act on ion movement: 1. Concentration gradient, and 2. Electrical gradient.
When these forces are equal then the ion (x) has reached its electrochemical equilibrium and no net movement of ion x will occur. If you measure the voltage inside the cell, you get the equilibrium potential for ion x.

57
Q

What is Nernst Equation?

A

Used to calculate the equilibrium potential.
Conditions:
- membrane is permeable to 1 ion
- there must be a concentration gradient for the ion
Ex = [RT/FZx] x ln ([x]outside /[x]inside)
Ex: equilibrium potential for ion x (mV)
R: gas constant, T: absolute temp (k), F: faraday’s constant (moles of electron charge), Zx: valence for ion x (K+=1, Na+=1, Cl-=-1, Ca2+= 2)

58
Q

What are some of the electrical potentials of common ions?

A

EK+ = -90 mV
ENa+ = + 60 mV
ECl- = -70 mV
This is the electrical potential (mV) required to apply to the inside of the cell in order to prevent movement of an ion down it’s concentration gradient.

59
Q

What is Goldman equation?

A

Because the membrane is permeable to a variety of ions + permeability varies depending on the ion, can’t use the Nernst equation to calculate RMP. Each ion will affect the RMP depending on its permeability + its concentration gradient - this is why we use Goldman equation.
Membrane potential = RT/FZ [log (Pk+ [k+]o + Pna+ [na+]o + Pcl- [cl-]i) /(Pk+[k+]i + Pna+[na+]i + Pcl-[cl-]o))]
Can swap the constants for 61.5
*Shows the important ions and their concentration gradient as well as shows the degree of importance of each ion at a particular time is proportional to membrane permeability at that moment (these are important when we consider action potential - neurons change permeability)

60
Q

Describe excitable cells

A

Excitable cells (like nerve cells and muscle cells) are capable of generating electrochemical impulses at their membranes.

61
Q

Define action potential (AP)

A

Rapid reversal of the resting membrane potential (as high as +45 and as low as -90mV). Action potentials are unidirectional. When excited action potential starts @ axon hillock down axon, to the terminal end (synapse). Axon hillock has special channels (voltage gated).

62
Q

Define threshold

A

The minimum voltage (membrane potential) to initiate action potential. Magnitude of the depolarization required to initiate an action potential (AP) at the axon hillock. At the threshold, the depolarizing forces must overcome the natural stabilizing forces, which are trying to main -70 mV.

63
Q

Define depolarization

A

The cell becomes more positive than the resting membrane potential (RMP) - anything higher than -70mV
*Changes in membrane potential require changes in membrane permeability - requires special membrane protein channels

64
Q

Define repolarization

A

Cell returns to the RMP

65
Q

Define hyperpolarization

A

The cell becomes more negative than RMP

66
Q

Describe gated ion channels. What are the three types of gated ion channels?

A

Open by a stimulus. Not leaky - can’t pass through if gates are closed.
1. Mechanically gated: deforming the membrane - press on cell membrane, movement stimulates opening
2. Chemically (ligand) gated: a chemical binding the channel (neurotransmitter, e.g. acetylcholine) - located @ dendrites, receive info.
3. Voltage gated: voltage changes in cell open channel (changes to membrane potential)

67
Q

Describe the diff voltage gated channels

A

Open when the cell membrane depolarizes.
Na+ channel is a fast voltage-gated channel that opens quickly, and closes quickly. Has an activation and inactivation gate.
K+ channel is a delayed rectifier K+ channel - still voltage gated with an activation gate - no inactivation gate.

68
Q

List the sequence of events (14) in an action potential

A
  1. “Stimulate” nerve
  2. Membrane depolarizes
  3. Action potential is initiated at -55 mV
  4. VG Na+ channels open very rapidly
  5. Na+ flows into cell
  6. Membrane depolarizes rapidly to +45 mV (inside of cell now has positive charge)
  7. K+ VG channels (delayed rectifiers) begin opening while Na+ VG channels begin inactivating - gives the AP a rounded peak
  8. Eventually all K+ VG channels open and all Na+ VG are inactivated
  9. K+ rushes out of the cell (repolarization)
  10. Membrane repolarizes (+45 mV to -70mV)
  11. K+ continues to leave the cell (K+ VG channels close slowly)
  12. Membrane hyperpolarizes (EK+= -90 mV)
  13. K+ VG channels close
  14. Membrane potential returns to normal (-70 mV) - VG channels return to “resting configuration” ready to fire another AP. *Chloride leak channels - leaves cell until -70
69
Q

Describe the clinical scenario of Tetrodotoxin poisoning, and what it has to do with APs

A

Emergency room patient (recently ate raw pufferfish) - numbness in the lips and mouth with profuse salivation, weakness in the limbs, severe headache, sweating, and severe nausea, vomiting, and abdominal pain.
- Puffer fish is known to contain tetrodotoxin (TTX), a powerful neurotoxin which reversibly blocks Na+ voltage gated channels - don’t get action potentials.

70
Q

Facts about the action potential. e.g. speed, amount of ions.

A
  • Relatively, very few ions move through membrane during an action potential. In 1 second, 10 million ions can diffuse through 1 ion channel. It takes 50 million ions to change the membrane potential by 100 mV. This is roughly one millionth of the ions available inside and outside the cell.
  • One AP will not affect concentration gradients
  • Na+ / K+ pump maintains concentration gradients and it is not required for repolarization
71
Q

Define the absolute refractory

A
  • No stimulus will excite the nerve
  • Caused by the inactivated Na+ channels
    *Another action potential is completely incapable of occuring
72
Q

Define the relative refractory period

A
  • Stronger than normal stimulus is required to produce an AP
  • Caused by hyperpolarized membrane (-90 to -55 requires strong stimulation)
73
Q

What do the refractory periods ensure?

A

Refractory periods ensure that the AP will travel in one direction - travels orthodromically. AP is all-or-nothing, once an action potential starts, it goes all the way to terminus.

74
Q

Describe sub-threshold potentials

A

Also called graded potentials.
- Do not produce AP
- Confined to local area of membrane (dendrites and/ or cell body of a neuron)
- Decays rapidly with distance and time from point of stimulus (ions that came in can leak out of cell again as graded potentials travel toward the axon hillock)
- They are not propagated (does not travel)
- Magnitude of response is proportional to the magnitude of the stimulus - graded e.g. can distinguinsh between diff magnitudes of touch
- Sub-threshold potentials can be summed at axon hillock (could reach threshold)
- Can be depolarizing (excitatory post-synaptic potential EPSP) or hyper-polarizing (inhibitory post-synaptic potential IPSP) - EPSPs and IPSPs can happen simultaneously in a neuron

75
Q

Describe current

A

Current is the rate of movement of charge. During AP, current is carried by positive ions such as Na+ or K+. Current flows from positive to negative.

76
Q

How is propagation down myelinated neurons different?

A

Myelin is an insulating material composed mainly of lipids (80%) and proteins (20%) which wraps around the axon - acts as an insulator.
Comes from Schwann cells (PNS) and oligodendrocytes (CNS). Myelin increases resistance across membrane by a factor of 5000 - no ion leakage out of axon. AP propagated much faster in myelinated neurons.
*APs can also happen faster based on the diameter and length of the axon - faster with larger diameter (less resistance)

77
Q

Describe the nodes of Ranvier

A

Gaps - exposed to outside environment.
Na+ and K+ VG channels located just under the edge of the myelin at nodes of ranvier.

78
Q

Describe saltatory conduction

A
  • Much faster than AP propagation in non-myelinated axons
  • Conserves energy: fewer Na+/ K+ ATP pumps required along axons since concentration gradients change mainly at nodes
    -BUT susceptible to demyelinating diseases like Multiple Sclerosis
79
Q

Describe the chemical synapse

A
  • The AP stimulates VG Ca2+ channels to open at the neuron terminus
  • Intracellular Ca2+ acts as a signaling molecule to cause mobilization of vesicles containing neurotransmitter
  • Fusion of vesicle to pre-synaptic membrane
  • Neurotransmitter is released by exocytosis into the chemical synapse
  • Binding of the neurotransmitter to a ligand-gated ion channel on the post-synaptic neuron