PHYS20008 - HOMEOSTASIS [Week 1]

What’s the main function of a cell

To make proteins

What do proteins do and what’s the importance of their shape?

Essentially everything. Proteins have specific shapes which allow them to interact with other structures in cells and so as long as they maintain their shape, they can do their job.

How do proteins get their shape?

• covalent bonds = primary structure

• H bonds = 2ndary or tertiary structure

Tertiary and quaternary structures held together by H bonds gives shape of proteins.

What disrupts H bonds?

Heat energy, pH & ions (body must regulate these in order to maintain optimal environment for cell function. - which is the purpose of homeostasis)

What are ‘disease states’?

When internal env drifts away from optimal conditions (heat energy, pH and ions)

Where does the energy that’s needed to make proteins come from?

Comes from cell resp (glucose and oxygen IN, CO2 and H2O OUT)

List 2 purposes of Homeostasis:

1) Body must regulate heat energy, pH and ions to maintain optimal env for cell function.

2) To provide adequate substrate delivery to maintain cell resp for energy for protein fuction

What are the 2 sides of an epithelial cell?

APICAL MEMBRANE - faces lumen (outside space)

BASEMENT/BASAL SIDE - faces inside of body & underlying tissue

How do water soluble substances cross membrane

They use passive processes like diffusion, facilitated diffusion (has transport proteins.

• travel down conc gradient (high conc to low conc)

What is the function of ATP synthase?

Consumes ATP and catalyses reaction of ATP = ADP + Pi + Energy

What are the properties of membrane?

semi permeable/antipathic/hydrophobic barrier

Definition of Homeostasis:

Maintenance of a RELATIVELY constant internal env which is essential for survival of each cell.

Describe reflex/feedback loop using the ex// of fall in bp:

1) Stimulus (ex//fall in bp) → 2) Sensor/receptor detects change → 3) Afferent pathway (sensory): carries info from receptor to integrating centre → 4) Integrating centre (usually brain/spinal cord): compares current state VS normal set point & decides if action is needed → 5) Efferent pathway (motor): carries instructions from integrating centre to effector → 6)Effector/Target: muscle/gland that performs the action / response that corrects imbalance & restores homeostasis

Why is the negative feedback?

In order to return back to homeostasis, reflex response must be completely turned off (response reverses the original problem).

2 classifications of reflex responses:

• Can be endocrine (hormone)

• Can be neural (Autonomic nervous system)

3 Types of reflex responses:

1) Simple endocrine reflex: internal/external change (stimulus) → endocrine cell detects that change (acts as both a sensor and integrating centre) → Efferent signal → Effector → Response occurs

• ex// beta cells of pancreatic islets wherein the efferent signal would be hormones released into blood and effector would be hormone reaching target tissue

2) Simple neural reflex: Stimulus → Activates receptor → Activates afferent pathway (sends info to brain) → neural integration occurs within CNS → efferent: output comes thru neuron → synapses onto effector → response occurs

3) Complex neuroendocrine reflex: Stimulus → activates receptor → activates afferent pathway → activates integration (within CNS) → allows neurons to secrete chemical signalling molecule into blood (becomes endocrine hormone - efferent) → endocrine hormone targets another integrating pathway → leads to release of a 2nd hormone (efferent signal 2) → produces downstream response

What’s the importance of beta cells?

Beta cells are:

• sensor

• integrator

• effector

ALL IN ONE CELL.

What is a positive feedback loop?

(also known as amplification responses): stimulus → activates reflex → amplifies stimulus

• ex// myometrial contractions during birth, oestrogen release during ovuation, Na channels in action potential

Can a positive feedback loop maintain homeostasis?

No because they amplify deviations from the set point, pushing systems away from stability rather than reversing changes.

What is the movement of diffusion (high conc to low conc) governed by?

Concentration gradient (difference between no of molecules on one side of barrier to other side of barrier)

What factor will restrict movement of diffusion?

How freely molecule can move across barrier.

What type of energy is conc gradient?

Potential energy

Where does the E that drives movement of diffusion come from?

From turning potential E to kinetic E.

What does diffusion do to conc gradients?

It eliminates them by causing a net movement of particles from areas of high concentration to areas of low concentration.

What substances does cell membrane allow & not allow to pass thru?

The cell membrane is a hydrophobic barrier so:

• allows lipid soluble stuff, bipolar covalent molecules like H2O and gases to cross

• doesn’t allow strongly charged molecules (like ions)/largely H2O soluble molecules (like proteins) to cross

What does penetrating and non penetrating mean?

• penetrating = can cross cell membrane

• non-penetrating = can’t cross cell membrane

What is osmolarity and tonicity?

• Osmolarity: total conc of all solutes (penetrating and non penetrating)

• Tonicity: relative conc of only non penetrating solutes (ex// ions and proteins)

  • Its always in reference to extracellular non penetrating solute conc compared to cells non penetrating solutes

  • tells abt movement of water into/out of cell

What is osmotic equilibrium?

Water still moves, but equally in both directions, so there’s no overall change in volume.

What does Fick’s law of diffusion describe?

Describes how easily/rapidly molecules move across cell membrane.

What is membrane potential?

The stored energy by having concentration/electrical gradients across a membrane.

Important Ion Distributions

Potassium

• HIGH concentration INSIDE the cell

• LOW concentration OUTSIDE the cell

Sodium

• HIGH concentration OUTSIDE the cell

• LOW concentration INSIDE the cell

Calcium

• HIGHER concentration OUTSIDE the cell

Chloride

• Major anion OUTSIDE the cell

Phosphates

• Major anion INSIDE the cell

Proteins

• Very high concentration INSIDE the cell

• Proteins become anions

What makes up extracellular fluid (fluid outside cells)?

Plasma (fluid part of blood that contais water, cations, anions and dissolved proteins) & Interstitial fluid (fluid immediately surrounding cells).

What does the isotonic principle say?

• For every cation in a solution, there must be an anion balancing it.

  • sodium outside is balanced mainly by chloride & bicarbonate (a major extracellular ion that also acts as a pH buffer)

  • Potassium inside is balanced mainly by proteins and phosphates

How do proteins and ions move across the membrane?

• Proteins are large negatively charged mols so they leave via exocytosis

• Ions move through ion channels (protein channels)

At rest, why does more potassium leave the cell than sodium enters?

Because the membrane is very permeable to potassium and relatively impermeable to sodium. This means there’s more potassium leak channels.

If potassium keeps leaving and sodium keeps entering, how do they not just equalise. So how do concentration gradients stay maintained?

Due to the sodium potassium ATPase/pump/ It actively pumps potassium IN and sodium OUT using ATP.

What is equilibrium potential (a.k.a reversal potential)?

It’s the membrane voltage where the forces on an ion are balanced. (when net ion movement = 0)

What are the equlibrium potentials for potassium & sodium & what’s the RMP?

• Ek = -90mV (meaning potassium whats memb potential to be -90 mV)

• ENa = +60 mV (meaning sodium whats memb potential to be +60 mV)

• RMP = -70 mV

Definitions of hyperpolarisation & depolarisation:

• Hyperpolarization: membrane potential becomes MORE negative.

• Depolarization: membrane potential becomes LESS negative / more positive.

Which Ion Has More Driving Force?

At RMP, Na is farther from its equilibrium potential than potassium is, so sodium has stronger force driving movement.

BUT, more potassium moves because membrane permeability to potassium is much greater.

What happens at threshold potential?

At threshold potential, many more sodium channels suddenly open, which dramatically increases sodium permeability.

• So membrane potential rapidly moves toward sodium equilibrium potential which creates depolarisation & forms the rising phase of the action potential.

Action Potential Sequence:

• Resting membrane potential (~−70 mV)

• Threshold potential reached

• Sodium channels open

• Sodium rushes in

• Depolarization

• Sodium channels close

• Potassium channels open

• Potassium rushes out

• Repolarization

• Return to resting membrane potential

What is the Nernst equation used to calculate & whats the formuls?

Used to calculate the equilbrium potential based on ion conc.

Formula: E_ion​ ∝ ln([ion]_outside / ​[ion]_inside​​)

What are the key takeaways from Nernst Equation?

• If outside concentration = inside concentration:

  • ratio = 1 means In(1) = 0, so equlibrium potential = 0

• If Outside > Inside:

  • ratio > 1, so equilibrium potential becomes positive (ex//sodium)

• If Inside > Outside:

  • ratio < 1, so equilibrium potential becomes negative (potassium)

Function of dendrites in neurons:

Receive signals (like antenna)

What’s significant about dendrites & cell bodies?

ONLY produce graded potentials. NOT action potentials.

What does graded potential mean?

Change in membrane potential LESS than threshold.

Important Features of Graded Potentials

1. Size proportional to stimulus: Bigger stimulus → bigger graded potential

2. Can move in BOTH directions

3. Amplitude decreases with distance: meaning it degrades which is why its called graded potential

How do graded potentials spread?

Sodium channel opens = sodium enters & positive.

Positive charge repels nearby positive charge. So positive charge spreads along dendrite, but signal gets weaker with distance.

What’s the function of axon hillock?

It connects cell body to axon. It’s also usually the trigger zone (site where action potential is initiated, except in primary sensory neurons).

Function of axon:

Where action potentials occur (action potentials travel down axon)

Function of axon terminals:

They contain & release neurotransmitters (chemical signalling molecules)

What is threshold potential?

Minimum membrane potential needed to initiate action potential.

What is the special property of axons?

They have voltage gated ion channels which open/close in response to voltage (membrane potential).

What are the 3 tyoes of voltage gated ion channels:

• Voltage-gated sodium channels

• Voltage-gated potassium channels

• Voltage-gated calcium channels

What are the 3 states of voltage gated sodium channels:

1) Closed: It’s closed at resting membrane potential, so no sodium flow.

2) Open: Open at threshold, so sodium enters cell and membrane depolarises.

3) Inactive: Inactivation gate blocks pore, so no sodium flow possible.

• Inactive state creates Absolute refractory period, meaning channel CANNOT open. It must return to closed state first in order to open again. This limits firing rate.

What are the 2 states of Voltage-Gated Potassium Channels?

1) Open

2) Closed

There’s no inactivation gate.