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Class notes Principles of Mammalian Physiology (PHGY215)
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Comprehensive class notes for PHGY 215.
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Module 1 - Homeostasis and the Basis for Excitable Cells:Introduction to Systems, Physiology and Homeostasis:
Most homeostatic control systems include three components:
1. Sensor: Detects environmental variables
2. Integrator: Compares the detected variable to it’s set point
3. Effector: Responsible for initiating the changes to restore the variable back to it’s set point
There are two types of homeostatic regulation:
Intrinsic Control:
Also referred to as local regulation or auto regulation. With intrinsic motivation, the three components
are all located within a tissue so the tissue can regulate its own internal environment. An example of this
is skeletal muscle dilating its blood vessels when it needs more oxygen.
Extrinsic Control:
The regulatory mechanisms are outside of the tissue. Most control systems in the body are extrinsic.
Membrane Physiology:
The plasma membrane is essential for the cell’s survival, maintaining homeostasis and engaging with
other cells. There are many components to the membrane:
- Phospholipids: The main component of the bilayer
- Cholesterol: Helps keep the membrane fluid
- Membrane proteins: Maintain cell function and structure. Facilitate nutrient transport
- Ion Channels: Allow ions to enter and exit
- Carbohydrate Chains: Receive signals from other cells
Cell to Cell Adhesions:
Allows cells to form tissues by connecting to one another. There are a few different ways cells can
interact with one another:
Extracellular Matrix:
The ECM is a network of proteins outside of cells bound in a carbohydrate gel. This gel-and-protein mix
allows cells to stay in place even if they are not physically touching. The three main proteins in the ECM
are Collagen, Elastin, And Fibronectin.
Cell Adhesion Modules:
CAM’s are typically transmembrane proteins that bind with other proteins extracellularly. They are
involved in protein-protein interactions with the ECM or CAM’s from other cells.
Cell Junctions:
Cells can also form junctions between themselves.
- Desmosomes: Form plaques of cadherins that act like cellular Velcro.
, - Tight Junctions: Form very tight seals between cells, preventing molecules from moving from
cell to cell.
- Gap Junctions: Six connexins form a connexon on a cell. When the connexons on two cells align
it forms a tunnel known as a gap junction. These tunnels are very small, and only small, water-
soluble particles can pass through.
Osmosis:
The effect of water flowing through a permeable membrane to reach concentration equilibrium. Water
does this because of osmotic pressure. The opposite force to this is hydrostatic pressure, which wants
water at an equal volume.
Equilibrium = Osmotic pressure (concentration pressure) – Hydrostatic pressure (Volume pressure)
Carrier Mediated Transport:
This uses ATP to maintain concentrations against a gradient. There are three characteristics that
influence mediated transport:
1. Specificity: Each protein is designed to recognize a certain type or group of substances
2. Saturation: Transport maximum occurs when all proteins are in use
3. Competition: No substance can reach Tm if proteins are transporting multiple different
substances
Vesicular Transport:
The use of vesicles to move substances into (endocytosis) or out of (exocytosis) cells.
Endocytosis
- Pinocytosis: A vesicle forms non-selectively, grabbing a section of ECF and bringing it into the
cell
- Receptor-Mediated Endocytosis: Like pinocytosis, but only activates when a target molecule
binds to the site. This ensures a specific molecule is in high concentration.
- Phagocytosis: Eating other cells. The pseudopods surround the target, which is then enclosed in
an endocytic vesicle, before being destroyed by lysosome enzymes.
Exocytosis:
Allows the release of large polar molecules from the cell. It also allows the cell to move proteins and
place them in the membrane. This is facilitated by the Golgi apparatus.
Membrane Potential:
Ion Extracellular (mM) Intracellular (mM)
Na+ 150 15
K+ 5 150
Ca2+ 2 0.0001
A- 0 65
Cl- 100 4
,Ions are unable to cross the plasma membrane without help. This allows the cell to create
electrochemical gradients. This gradient creates what is known as membrane potential, which all cells
have to some degree. Excitable cells like neurons and muscle cells utilize this membrane potential to
facilitate bodily functions. The potential can be calculated using the formula:
Voltage ( V )=Current ( I )∗Resistance ( R)
Resistance is dependant on if Ion gates are open or closed. If they are closed, resistance is high and
current is low.
Ion Channels:
Large, transmembrane proteins that allow ions to enter or exit cells, generally down their gradient.
Voltage-Gated:
These open and close in response to changes in membrane potential.
Chemically Gated:
Open when exposed to a specific chemical messenger (ligand)
Mechanically Gated:
Open in response to mechanical deformation such as stretching.
Thermally Gated:
Open when exposed to temperature changes.
The Nernst Equation:
Simply put, the electrochemical gradient is as follows:
Electrochemical Gradient=Concentration Gradient + Eletrical Gradient
Difficultly put, it is this:
( R∗T ) Co
E=2.3026∗( ) log ( )
( z∗F ) Ci
Where:
E= equilibrium potential (Energy where there is no net flow) for an ion in mV
R= Universal gas constant T=Absolute Temperature in K
z=valence of ion F= Faraday Constant
C=concentration outside and inside the cell in mM
, 61 Co
This can be simplified to E= log ( )
z Ci
If the membrane potential is greater than the equilibrium potential, ions flow out of the cell if it is less,
they flow into the cell.
Resting Membrane Potential:
This is dependent upon the types of ion channels found in the membrane, the concentration on both
sides of the membrane, and their relative permeabilities at that time. This can be calculated with the
Goldman equation:
61 Pna∗Nao+ Pk∗Ko+ Pcl∗Cli
Vm= ∗log ( )
z Pna∗Nai+ Pk∗Ki + Pcl∗Clo
Making sure to add each ion that has a channel in the cell.
Graded Potential:
Local changes in membrane potential used for signaling. A change in potential from -70mV to -60mV
represents a 10mV graded potential. These are generally caused by triggering events that activate
voltage-gated ion channels. While it can spread along the membrane, it quickly loses strength and
disperses.
Ionic Basis of the Action Potential:
Like graded potentials, action potentials are caused by a triggering event or stimulus that results in
localized depolarization. However, action potentials propagate throughout the entire membrane and do
not lose strength. The trigger event must be sufficiently large to trigger an action potential, they are “all
or none” reactions. The magnitude of the event must cross the threshold, after which the cell undergoes
rapid depolarization to the point where the membrane potential becomes positive. The membrane then
rapidly repolarizes and can overcompensate with an after hyperpolarization before returning to RMP.
This happens because Na+ gates open, drastically increasing sodium permeability for a short time. The
gate then become inactive, known as the refractory period, stopping sodium flow, and moving the
membrane potential back toward K+. The Na-K-ATPase pump becomes very active during this phase to
restore concentration gradients.
Nerves and Synaptic Transmission:
Neurons have four functional zones that are involved in the transmission of neural impulses:
1. Input Zone: Where incoming signals are received. Contains Dendrites and Cell body
2. Trigger zone: Where action potentials are initiated. Contains Axon Hillock
3. Conductions Zone: Where action potentials are conducted to their target locations. Contains
Axon.
4. Output Zone: Part that releases chemical messengers. Contains Axon terminals.
The initial action potential triggers a new action potential in each subsequent zone. This allows the
signal to travel without decay. Refractory periods ensure that this chain reaction is one way.
- Absolute Refractory Period: No action potentials may occur
- Relative Refractory Period: A strong enough trigger can start a second action potential
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