Membrane Transport Part 2

Osmosis

• movement of water across the cell membrane

• helps maintain fluid and electrolytes balance

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Fluid Balance

 maintaining the proper amount and distribution of water in the body

Electrolyte Balance

maintaining appropriate concentrations of dissolved ions, such as Na⁺, K⁺, Cl⁻, and Ca²⁺, in body fluids.

Aquaporiins

 allows the rapid passage of water, while blocking the passage of ions

How does aquaporin block out ions

• The pores are too narrow for hydrated ions to enter the channel (.e. Na+ , K+, Cl- , Ca 2+)

• Aquaporins are particularly impermeable to H+ as a hydronium ions (H3O+)

• These ions diffuse through water fast

• This relay mechanism  requires Moving and breaking the bonds between adjacent water molecules
  
  

What distinguishes ion channels from aqueous pores

1. Ion selectivity

2. Ion channels are not continuously open

Structure of a neuron

membrane potential

A voltage difference across the plasma membrane

Resting membrane potential of a neuron

 steady voltage difference across the neuron’s plasma membrane (usually -70mV)

Why is the cell more negative inside

 because of negatively charged proteins inside the cell and greater permeability of the membrane to K+ (i.e. leaky K+ channels, K+ ions move dow the gradient out the cell)

Voltage gated Na+ channels

• Tetramer of 4 identical polypeptide chains

• Each domain has a voltage sensor (contains unusual transmembrane helix with many positively charged amino acids).

• When membrane is polarized, charged helix exposed to negatively charged cytosolic side of membrane

• Depolraization: helices experience electrostatic force. Helices expose charges to extracellular side of the membrane (opens channel)

Open Na+ channels

• depolarization

• Channels open in response to stimuli 

• A small amount fo Na+ enters the cell, down its electrochemical gradient 

• This influx of positive charge depolarizes the membrane even more, opening more Na+ channel (self amplification-> positive feedback) 

Closed Na+ channels

• A sufficient depolarization causes voltage gated NA+ channel  

• Na⁺ enters the cell down its electrochemical gradient. 

• The influx of positive charge depolarizes the membrane further, opening more Na⁺ channels through positive feedback. 

• This produces the rapid rising phase of the action potential.
  

Inactivated Na+ channel

• Unable to reopen, until after the membrane potential until after initial negative value 

• After opening briefly, Na⁺ channels automatically become inactivated, even if the membrane is still depolarized. 

• Na⁺ can no longer pass through the channels. 

• Meanwhile, voltage-gated K⁺ channels open, allowing K⁺ to leave the cell and repolarize the membrane. 

• The Na⁺ channels remain inactivated until the membrane potential returns sufficiently toward its resting, negative value. They can then return to the closed state and become available to open again. 

NA+ ion transport after depolarization

• Voltage-gated Na+ channels open in response to a stimulus

• A small amount of N+ enters the cell, down its electrochemical gradient

• The influx of positive charge depolarizes the membrane further, and opens more Na+ channels (self-amplification, positive feedback), from -70 mV to +40 mV

• At this point, net electrochemical driving force for Na+ is zero, cell would come to new resting state (with all Na+ channels open).

•  What saves cell from spasm?
  Chat: voltage-gated Na⁺ channels become inactivated, and voltage-gated K⁺ channels open to repolarize the membrane. 

Action Potental

1. Resting potential: The neuron is at about −70 mV; voltage-gated Na⁺ and K⁺ channels are closed.

2. Threshold: A stimulus depolarizes the membrane enough to trigger an action potential.

3. Depolarization: Voltage-gated Na⁺ channels open, and Na⁺ rushes into the cell, making the inside more positive.

4. Repolarization: Na⁺ channels inactivate, and voltage-gated K⁺ channels open. K⁺ exits, making the inside more negative.

5. Hyperpolarization: K⁺ channels close slowly, so extra K⁺ exits and the membrane briefly becomes more negative than resting potential.

6. Return to resting potential: K⁺ channels close, and the membrane returns to its resting state.

Na⁺ goes in → depolarization; K⁺ goes out → repolarization.

When can a membrane fire a second action potential?

only after the refractory period ends

Absolute Refractory Period

• when all Na+ channels are in the inactivated state and can’t open, regardless of how strong the stimulus is.  

• From the beginning of depolarization until the early repolarization phase of the action potential  

Relative refractory period  

• From late repolarization until hyperpolarization, until na+ channels have fully recovered and membrane conductance returns to resting levels 

• Some Na+ channels have recovered , but K+ channels remain open, making the membrane more negative than at rest (hyperpolarization  

• A stronger than normal stimulus is required to reach threshold

What is the purpose of K+ channels in action potential

To restore the negative membrane potential needed for another action potential

What causes hyperpolarization of the membrane

K+ channels are slow to close, leaky channel causes the cell to more negative than normal resting potential (hyperpolarization)

How does the membrane return to resting membrane potential

• Voltage gated K+ channels close

• Na+/K+ pum: restores sodium and potassium gradients

Unidirectional propagation

Propagates in one direction along the axon because the region of the membrane that just fired an action potential is in its refractory period

• Depolarization: Na⁺ enters the axon, triggering an action potential.

• Spread: Positive charge spreads to the adjacent region, bringing it to threshold and triggering another action potential.

• Refractory period: Behind the action potential, Na⁺ channels are inactivated and K⁺ exits the cell.

• Unidirectional propagation: The region behind cannot immediately fire again, so the action potential moves forward along the axon.

Channelrhodopsins

• Photosensitive ion channel 

• When neurons are exposed to blue light, these channels open , depolarizing  and activating cells 

• Optogenetics

Optogenetics

a technique that uses light-sensitive proteins to control and study the activity of specific cells, particularly neurons, with high temporal and spatial precision.

Structure of a CTFR Protein

Large glycoprotein  found at cell membrane

Found in epithelial cells -> specialized cells that cover the internal and external body surfaces

What areas of the body are most affected by cystic fibrosis? Where is CTFR found

• Skin, lungs, and digestive tract

• Found in the digestive tract

What makes CFTR a “unique” ABC transporter?

• uses the energy from ATP hydrolysis in the opening and closing of a channel

• CFTR functions as an ATP-regulated Cl⁻ channel, allowing chloride ions to pass through the membrane down their electrochemical gradient.

Normal function of CTFR protein

• Allows the release of Cl- from the cell → changes the regulation of water in epithelial cells → releases water and creates mucus

• Lack of Cl movement causes lack of H20 movement

• Helps establish ion concentration gradient that regulates water movement by osmosis.

Defective CTFR Protein

• In the airways, defective CTFR reduces chloride secretion and can increase sodium absorption, decreasing water content on the airway surface

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Why do CTFR mutations cause thick mucus

mutated protein doesn’t push cl- out fo cells → water isn’t removed from cell either → mucus becomes thicker → harder to breathe and for cilia to remove bacteria

What happens to mucus secretion in the pancreas and lung when the CTFR gene is mutated

Thick mucus secretions in the pancreas and lungs → digestive enzymes are not able to reach the small intestine

Symptoms of CF

• Chromic pulmony (lung) disease

• Thick secretion in airway passages

• Breathing problems 

• Coughing/ wheezing 

• Pancreatic insufficiency

• Excessive appetite but poor weight gain

• Greasy blot stools 

• Saltier sweat

• Meconium ileus

Meconium ileus

neonatal small‑bowel obstruction caused by abnormally thick, sticky meconium blocking the terminal ileum, and it is strongly associated with cystic fibrosis, occurring in most affected infants

How is cystic fibrosis diagnosed

• Detection of  meconium ileus at birth

• Check blood samples for IRT (immunoreactive trypsinogen)

• Sweat test

• Genetics test

Why do we use a sweat test?

less salt is reabsorbed from sweat into sweat gland in person with Cystic Fibrosis

Treatments for Cystic Fibrosis

• Antibiotics

• Vibrating vests or bronchodilators to loosen mucus so it can be cleared]

• Medications with digestive enzymes

• In severe cases, you can do a lung transplant

• Targeted Therapy based on CFTR gene mutation

What do CTFR drugs do

help CTFR protein reach the plasma membrane to function

Prevents both Cl- ions and water from leaving lung epithelial cells

mutation in the CFTR protein in lung epithelial cells