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Homeostasis and Body Fluid Compartments Learning Objectives: - Define physiology - Define homeostasis - Describe negative feedback control systems - Explain the components of a negative feedback loop and their roles in maintaining homeostasis - Describe the distribution of bodily fluids - Report the...

Description

Homeostasis and Body Fluid Compartments Learning Objectives: - Define physiology - Define homeostasis - Describe negative feedback control systems - Explain the components of a negative feedback loop and their roles in maintaining homeostasis - Describe the distribution of bodily fluids - Report the chemical composition of the intracellular fluid, interstitial fluid and plasma in terms of ion and protein distribution - Draw a diagram and label the ion composition of the inside versus the outside of the cell - Label the organelles of the cell and their functions - List three main functions of the cell membrane - Draw and label a phospholipid molecule - Label a diagram of the cell membrane including membrane-associated proteins Physiology  study of the normal functioning of a living organism and its component parts - Chemical level - Cellular level - Tissue level - Organ level - Body system level - Whole body The cells in a multicellular organism play a critical role in the homeostasis of the organism as a whole. Numerous organ systems are continuous with the external environment - Respiratory - Digestive - Urinary - Reproductive Homeostasis  Ability of the body to maintain a relatively constant internal environment; Dynamic & regulatory process Negative feedback control systems monitor and respond to changes in the internal environment - Measure the existing value of some factor - Compare it to a selected set point value - Employ the difference of these 2 values to initiate a series of physiological changes that return the factor toward the set point value - Only negative feedback loops are homeostatic b/c they keep body at or near a set point

Cells within our body are surrounded by interstitial fluid which serves to act as a transition between the external environment, and the intracellular fluids inside cells. Intracellular fluid  Fluid inside the cell (cytoplasm) Extracellular fluid  Fluids outside of the cell = interstitial fluid + plasma Cell membrane is selectively permeable and contains transport mechanisms Functions: - Physical isolation  Separation of intracellular & extracellular environment - Exchange with the environment - Communication

Interaction of the Cell with its Environment Learning Objectives: - List 4 functions of membrane proteins - Describe the mechanisms or membrane transport - Define simple diffusion - Judge the statements regarding properties of the diffusion process as true or false - List and explain 6 factors that affect the rate of diffusion - Draw the process of facilitated diffusion and explain how facilitated diffusion is affected by competitive inhibition and limited transport capacity - Draw the process of active transport using the example of the Na+/K+ ATPase - Compare and contrast diffusion, facilitated diffusion and active transport - Outline ways in which cells can communicate localy with one another - Define Autocrine and Paracrine signals Messages the cell receives need to either be processed at the cell membrane or pass through the cell membrane in order to be interpreted. Functions of membrane proteins - Ion channels – Let ions into or out of the cell - Enzymes – Help catalyse reactions - Receptors – Message reception - Membrane carriers – Help transport big molecules into or out of the cell Selectively permeable  some molecules are able to cross the membrane and others aren’t Mechanisms of membrane transport - Endo/exocytosis – phagocytosis of small molecules - Diffusion through lipid bilayer – lipophilic molecules - Diffusion through protein channels – hydrophilic molecules - Facilitated diffusion – large bulky molecules - Active transport  ATP dependent process that moves molecules against electrochemical gradient Simple diffusion  movement of molecules from an area of higher concentration to an area of lower concentration due to a molecule’s random thermal motion - Molecule size ↓size = ↑diffusion - Concentration gradient ↑concentration gradient = ↑diffusion - Membrane thickness (diffusion distance) ↑thick = ↓diffusion - Membrane surface area ↑S.A = ↑diffusion - Composition of lipid bilayer - Lipid solubility ↑Lipophilic = ↑diffusion

Diffusion of lipophilic molecules through the lipid bilayer Diffusion of hydrophilic molecules through protein channels (ion channels) - Protein mediated transport - Ion channels can be selective due to charge & size - Still simple diffusion, just through an ion channel - Factors o Concentration gradient o Molecule size o Charge of molecule o Number of protein channels - Can move 10x more molecules than a carrier protein - Create a continuous passage between extracellular & intracellular fluid Facilitated diffusion  Some molecules are too big to be transported by protein channels. They are also unable to pass through the membrane due to their chemical properties. Therefore, need carrier proteins to carry them across - Protein mediated transport - Chemical specificity - Competitive inhibition - Limited transport capacity - Saturation – all the transporters are working as fast as possible - Never create a continuous passage between extracellular & intracellular fluid Na+/K+ ATPase - Pumps 3 Na+ out and 2K+ in for every molecule of ATP - Found in plasma membranes of all animal cells - Key transporter protein in regulating & maintaining the Resting Membrane Potential - Maintains high [Na+] in extracellular fluid & high [K+] in intracellular fluid o Recall: Salty (Banana) o If the Na+/K+ ATPase was absent, K+ would leave and Na+ would enter until electrochemical equilibrium was reached and no further net movement of ions occurred.

Selective? Competitive inhibition? Goes with concentration gradient? ATP required?

Diffusion Lipophilic Hydrophilic No Yes No No

Facilitated Diffusion Yes Yes

Active transport Yes Yes

Yes

Yes

Yes

No

No

No

No

Yes

Long distance communication Endocrine system – Hormones to communicate with target cell Nervous system - Neurotransmitters – Chemical signals with local and fast effect - Neurohormones – Signals that need to travel the blood stream in order to affect the target cell Local communication - Chemical mediated Cell-Cell communication o Cytokine  Chemical signal made by any type of cell in response to stimulus o Autocrine signal – Signal that acts on the cell that made it o Paracrine signal – Signal that acts on neighbouring cells -

Contact-Dependent signals  Surface proteins on one cell bind to surface proteins on another cell

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Gap junctions o Connexins (protein channels) make “bridges” between cells o Direct transfer of chemical and electrical signals

Osmosis, Tonicity & the Resting Membrane Potential Learning Objectives: - Define osmosis and osmotic pressure and describe the factors which affect the movement of water across membranes - Define osmol and Osmolarity. What is the osmolarity of body fluids? - Define tonicity, and explain the differences between isotonic, hypotonic and hypertonic solutions - Explain the effects of isotonic, hypotonic and hypertonic solutions on cells - Describe how chemical and electrical gradients affect the movement of molecules across membrane - Define a resting membrane potential and state its normal polarity. Name the cells in the body with a resting membrane potential. - Demonstrate how a membrane potential can arise from diffusion starting with equal molar solutions of NaCl and KCl separated by a membrane when the membrane is permeable only to K+ - List two factors that affect the cell’s membrane potential - Discuss two functions of the Na+/K+ pump in terms of the resting membrane potential Osmosis  Net movement of water down its concertation gradient - Water moves to dilute the more concentrated (↑osmolarity) solution o Solution that has ↑[solute] has ↓[H2O] o Solution that has ↓[solute] has ↑[H2O] - Osmosis across a cell membrane is affected by o Permeability of the membrane o Concentration gradient of solutes o Pressure gradient across cell membrane Osmotic pressure  Pressure applied to exactly oppose the osmotic movement of water - Amount of osmotic pressure exerted by a solute is proportional to the concentration of the solute in the number of molecules or ions Osmolarity  # of particles (ions or molecules) per litre of solution - Unit: osmole/L) - Size/composition of particles is IRRELEVANT - Osmolarity (# of particles, not molecules) is what is key for predicting osmosis - Need to know: o Number of moles of the substance in solution o Whether it dissociates in solution o Recall: Ions dissociate, molecules (e.g. glucose) do not. ▪ 100mM glucose = 100mOsm ▪ 100mM KCl = 200mOsm ▪ 200mM BaCl2=600mOsm

Tonicity  ability of a solution to cause osmosis across biological membranes - Osmolarity of body fluids = 300mOsm/kg of solution - Isotonic – Same osmolarity as body fluids = 300mOsm Cell stays the same - Hypotonic – Lower osmolarity than body fluids 300mOsm Cell shrinks

Electrochemical gradient - Chemical gradient – Molecules move from areas of high concentration to areas of low concentration - Electrical gradient – Electrically charged molecules (ions) tend to move towards areas of opposite charge If electrical and chemical gradients are in opposite directions, the ion will move down its electrochemical gradient until the electrical gradient force becomes equal in magnitude to its chemical gradient form (electrochemical equilibrium). Net movement of this ion across the membrane stops. Resting membrane potential – Electrical potential of a cell membrane resulting from the unequal distribution of a few ions - Very minute excess of anions accumulates inside the inner surface of the cell membrane - An equal number of cation accumulates immediately outside the membrane - Electrical potential across the membrane with the inside negative with respect to the outside - ALL cells have a membrane potential - Factors that affect the cell’s membrane potential o Concentration gradients of different ions across a membrane o Permeability of the membrane to these ion ▪ Very permeable to Cl-, K+ ▪ Not that permeable to Na+

Action Potential Learning Objectives: - Recognize the difference between excitable and non-excitable cells. - Draw a neuron and label the soma, axon, dendrites, axon hillock, myelin sheath, nodes of Ranvier, and axon terminals. Fill the blank statements relating the name of the structure with its function. - Define depolarization, repolarization, threshold, and hyperpolarization. - Compare and contrast action potentials and graded potentials - Draw a diagram of an action potential and the permeability changes of sodium and potassium and use it to describe the ionic mechanisms of the action potential - Explain how the axon hillock acts as the trigger zone in action potentials. - Outline the mechanism of action of the “voltage dependent” sodium and potassium channels. - Draw the voltage-gated sodium and potassium channels and interpret how the opening and closing of these channels permits action potential propagation Neurons use electrical signals in the form of action potentials to communicate with one another. They can carry this signal rapidly and over long distances Neuron Propagation of an electrical signal and release of neurotransmitters is what our body relies on for interaction with the environment

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Dendrites – Structures that receive the incoming signals from neighbouring cells Axon – Carry outgoing information Soma – All cellular processes (i.e. protein synthesis) take place here Synapse – Region where the axon terminal meets the target cell Myelin – formed by Schwann cells. Consists of multiple layers of cell membrane wrapped around segments of the axon Node of Ranvier – Gap between the two Schwann cells; Unmyelinated area Axon Hillock – Trigger zone of the neuron

Ion movement creates electrical signals RMP of a neuron is -70mv - At rest, the cell membrane is much more permeable to K+ than to any other ion o ∴K+ is the ion contributing most to RMP value - Cell is only slightly permeable to Na+ at rest o If we change permeability of cell to Na+, can change its electrical potential as well Depolarization – Cell becomes more positive than the RMP (Na+ enter cell) Repolarization – Depolarized membrane returns to the RMP (30mV >> -70mV) Threshold – Minimum depolarization that will initiate an action potential (-55mV) Hyperpolarization – a membrane potential that is more negative than the RMP In neurons, gated channels control the ion permeability of the neuron - Mechanically gated ion channels – Open in response to mechanical stimulation - Chemically gated ion channels – Open in response to chemical binding - Voltage gated ion channels – Open in response to voltage change Graded Potentials - Occur in the soma or dendrites of a neuron - Depolarization of hyperpolarization's caused by opening voltage-gated channels - "Graded" because the amplitude of potential is directly proportional to the stimulus strength o ↑Stimulus = ↑Potential - Travel only a short distance and signal loses strength over time due to o Current leak o Cytoplasmic resistance – ions getting resistance from fluid in cytoplasm - Important for short distance or local communication

Action Potential - At the axon hillock (deciding point aka trigger zone), if the depolarizing stimulus reaches threshold (-55mV), an action potential will be triggered and propagated down the axon - 3 important things about action potentials o "All or none" – If -55mV at the axon hillock, an AP WILL fire o Unidirectional – ALWAYS goes from axon hillock to axon terminals o Always the same amplitude & direction – Always reaches peak at ~+30mV -

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During the resting state, the permeability for K+ is 25-100X greater than that for Na+ o Greater leakage of potassium ions through the "leak" channels than sodium o K+ ions move OUT of the cell down its electrochemical gradient At the onset of the AP, the voltage-dependent Na+ channels open & increase the membrane permeability to Na+ about 500X o Na+ ions move INTO the cell down its electrochemical gradient o Influx of sodium causes the cell to become more positive = Depolarization Within a few fractions of a millisecond, the voltage-dependent Na+ channels are inactivated, returning sodium permeability to normal Membrane depolarization also causes voltage-dependent K+ gates to open but at a slower rate. o Increased potassium conductance doesn’t rise as high as sodium conductance but o Gates are also much slower to close o More potassium going out will cause the electrical potential of the membrane to become more negative than RMP = Repolarization >> Hyperpolarization

1. RMP – Permeability for K+ is 25-100X greater than that for Na+ 2. Depolarizing Stimulus 3. Threshold – Voltage-dependent Na+ channels open quick; Voltagedependent K+ channels open slow 4. Na+ into cell = Depolarization 5. Na+ voltage-dependent channels close, K+ fully open 6. K+ leaves cell = Repolarization 7. More K+ leaves cell = Hyperpolarization 8. Voltage gated K+ channels close 9. Neuron returns to RMP

The walls of channels contain oxygen atoms to which the dehydrated sodium and potassium can bind. The configuration of oxygen atoms lining the channels determines their specificity for either sodium or potassium. Voltage-Dependent Sodium Channels

Will open at a voltage of At RMP During depolarization During repolarization

Activation Gate -55mV

Inactivation Gate -70mV

Closed Open Open – Doesn’t close

Open Open Closed

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Absolute refractory period  Period where no other action potential will take place until these channels are back to their resting position Inactivation gate is responsible for the absolute refractory period and for the unidirectional propagation of the action potential

Voltage-Dependent Potassium Channel - The voltage-dependent potassium channel also begins to open during depolarization - The potassium channel is much slower than the sodium channel and its peak permeability occurs at approximately +30mV - The loss of K+ through the potassium channel is responsible for the hyperpolarization phase of the action potential

Propagation of the Action Potential and the Chemical Synapse Learning Objectives: - Sketch the propagation of an action potential down an axon terminal. - Discuss the all-or-nothing principle of action potential and stte its physiological significance in action potential propagation. - Discuss what determines the unidirectional nature of the action potential - List the two main factors that affect the velocity of conduction of an action potential down a nerve fiber. - Describe the process of saltatory conduction of action potentials. - Compare saltatory conduction to conduction on unmyelinated axons. What are the advantages of saltatory conduction? - Describe a disease that results from the loss of myelin. - Outline the events occurring at a chemical synapse, beginning with the arrival of the action potential in the pre-synaptic terminal Propagation of the Action Potential - At the peak of action potential, intracellular membrane is positive with respect to extracellular o Extracellular: Region of negativity draws off positive charges from the membrane ahead of and behind the action potential, causing current to flow towards the DEPOLARIZED region o Intracellular: Positive current flow repelled by the positive ions already in the cytoplasm & attracted by the negative charge of adjacent regions of the membrane - End result = Depolarization of the membrane ahead of and behind the action potential. - When the membrane potential of the adjacent membrane reaches threshold, voltage-dependent sodium gates open and an action potential is generated in the adjacent region. = - By repetition of this procedure, the action potential is propagated along the whole length of the axon without losing its strength. -

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All or nothing principle o Na+ voltage gated channels open at -55mV; o Threshold reached = action potential Unidirectional nature of AP is caused by the Na+ inactivation gate which prevents Na+ from entering during the absolute refractory period

Main factors that affect speed of action potential conduction down an axon - Diameter of the axon: ↑Axon diameter = ↑Faster conduction - Resistance of the axon membrane to ion leakage o ↑Ion leakage = ↓Slower AP o Myelin prevents ion leakage

Saltatory Conduction - Myelin  Multiple layers of cell membrane that wrap around and insulate axons o Avoids exposure of axon to extracellular fluid, preventing current from leaking out of the cell o Conduction is faster with myelin ∴Axons can have a smaller diameter - Saltatory conduction is the apparent "leap-frogging" of the action potential down myelinated axons - Unmyelinated nerve fibers conduct action potentials in a continuous wave down the nerve fiber membrane - Myelinated nerve fibers are insulated except at the Nodes of Ranvier - ∴Saltatory conduction ONLY involves membrane permeability changes at the nodes - Advantages of saltatory conduction are o Less current leak o Less resistance o Smaller axon diameters - MS is a disease resulting from the loss of myelin o The current is going to leak out, eventually causing enough of a difference that axon signals will not fire, and paralysis of these cells will occur Chemical Synapse - Information passes from cell to cell at the synapse - Synapse is composed of the axon terminal of the pre-synaptic cell and the plasma membrane of the post-synaptic cell - At axon terminals, depolarization triggers the release of neurotransmitters from synaptic vessels - Neurotransmitters then cross the synaptic cleft, and transmit information to the postsynaptic cell by opening chemical-gated channels

1. Depolarizing stimulus coming down 2. Voltage gated Ca2+ channels open, Ca2+ into the cell 3. Ca2+ cause vesicles to release neurotransmitters 4. Neurotransmitters bind to receptors on post-synaptic neuron 5. Ion cha...