Found 2.2 CM

Passive 3 vs Active Transport 1 Summary

speed is inverse to size

Passive Transport

• Diffusion = net movement down its gradient

• simple diffusion: S & M

• facilitated diffusion: L

• every transported substance moves down its own gradient

Active is the only one that has at least one substance going against it’s concentration gradient (CG)

CG vs EG 2 vs PG

concentration gradient (CG) truly the number of molecules

Electrochemical Gradient (EG)

• Electrical charge gradient created by the difference in charge across the lipid bilayer

• ions can move based on charge difference across membrane

• Originally the concentration gradient was equal, but now it is unequal & wants to achieve electoral neutrality

• Nernst Potential (equilibrium potential)

  • Basically just describes how electrical & chemical gradients oppose each other

Pressure Gradient (PG): unilateral increase in pressure can force solutes across caused by greater numbers of molecules striking the membrane per second on one side than on the other side

CG, EG, PG Visual and recap

motion = ?

direction vs net

osmosis

All molecules/ions in body fluids (including dissolved substances) are in constant motion that we call "heat"

Greater motion = more heat

Motion never ceases completely except in absolute zero

Molecules move in all directions, but here we are concerned with the NET movement of those molecules. So it’s not that molecules move ONLY from high concentration to low concentration areas. Rather, they move in both directions, but the NET movement is from higher concentration to lower concentration until equilibrium is attained.

Osmosis is similar to diffusion, except it’s the movement of water the solvent rather than solute

Diffusion: Lipid- vs. Water-Soluble thru CM?

Lipid-Soluble Substances

• Readily traverse through phospholipid bilayer

• Ex: oxygen, nitrogen, carbon dioxide, alcohols, VA etc.

Water-Soluble Substances

• Can readily traverse membrane through selectively permeable and gating membranous protein channels even if charged

  • Ex: Water is highly insoluble through membrane bilayer, but readily passes through protein channels (aquaporins) that penetrate through membrane

Voltage-Gated Na⁺ Ion Channels - 2

When the inside of the cell loses its negative charge (b/c more positive), VG-Na+ channel opens to allow Na+ to enter the cell as it flows down its concentration gradient (basic mechanism for depolarization and eliciting action potentials in nerves)

Selectivity filter lined with strong negative charges, pulling small dehydrated Na+ ions through channel

Na+ makes inside of the cell more positive

Voltage-Gated K⁺ Ion Channels - 2

3 step process

When the inside of cell is (+), K+ channels open to allow K+ to leave cell as it flows down its concentration gradient (basic mechanism for repolarization of cell)

Permit K+ ions passage through cell membrane ~ 1000x more readily than Na+ ions despite its larger size d/t inter-carbonyl oxygen distance on the inside of the protein.

K+ makes inside of the cell more negative

1. Hydrated K⁺ in body fluid is surrounded by water molecules—a hydration shell

2. Carbonyl oxygens temporarily replace the surrounding water molecules as it passes through the narrow filter.

3. Dehydrated K⁺ becomes surrounded by water again.

Ligand-Gated Channels - nAchR

Nicotinic Acetylcholine Receptor (nAchR)

• Involved in skeletal muscle contraction

• Ach binds nAchR, opens the gate, and allows Na+ ions to flow into the cell

• This influx of Na+ makes the inside of the cell more positive, bringing the membrane potential to threshold potential, and elicits an action potential (see action potential section for more detail)

• Ligand gated open → developed EPP → TP met → VG channels open

Other Types of Gated Ion Channels - 2

Carrier-Mediated: Facilitated Diffusion - ex

saturation kinetics 2

Water-soluble molecules cross cell membrane via carrier proteins

Example: glucose, fructose, galactose

Saturation kinetics

• Once at max rate (V_max), protein cannot increase transport rate, despite concentration of solute (it can't move solutes across any faster)

• For a good part until Vmax, facilitated diffusion is faster than simple diffusion

Carrier-Mediated: Active Transport

Primary vs Secondary

Uses energy to move at least one substance against its CG (uphill)

Requires ATP (energy) either directly or indirectly

Primary Active Transport

• Energy derived directly from ATP hydrolysis (or some other high-energy PO4)

• Na+/K+ pump, Ca+ pump, H+ pump

Secondary Active Transport

• Energy derived indirectly from ATP hydrolysis involved in an active transport process that formed an ionic concentration difference across membrane

• Basically, it piggybacks off an active transport process

Na-K-ATPase - define 3

secondary fx

Uses energy (ATP) to pump both Na+ & K+ against their concentration gradients

Moves 2 K+ into cell & 3 Na+ out of cell

Creates & maintains ionic gradient (Na+ & K+)

Establishes resting net (-) charge inside cell

• Also a secondary fx is to maintain the osmotic balance

• Controls cells volume and prevents bursting by pumping Na+ out of the cell (water follows Na+)

Na-K-ATPase Visual

5 steps

Phosphorylation –addition of a phosphate group following the hydrolysis of ATP which leads to a conformational change in the target protein.

1. 3 Na⁺ intracellularly binds first

2. Phosphorylation by ATP causes conformational change

3. 3 Na+ released extracellularly as 2 K+ binds to other site

4. Dephosphorylation favors original form

5. 2 K+ released intracellularly

Active Transport: Calcium Ions - 1 ex 2

Ca++ in ICF is normally very low (10,000x less than ECF)

Achieved by 2 active transport calcium pumps

• PMCA: In the cell membrane to pump Ca²⁺ out of cell

• SERS: Pumps Ca²⁺ into organelles such as the sarcoplasmic reticulum

Active Transport: Hydrogen Ions - ex 2

Gastric glands (hydrochloric acid)

• At the secretory ends of the gastric gland, H+ ion concentration is increased up to 1 million-fold along with Cl- ions to form hydrochloric acid

Renal tubules (pH buffer)

• Large amounts of H+ ions are secreted against its gradient (by 900-fold) from blood into renal tubular fluid for elimination

• Na/H exchanger is a 2nd active transport

Secondary Active Transport:

relies on which ion gradient?

Two Forms

Energy in the form of an ionic gradient created by a primary active transport process

Usually involves Na+ ion gradient created by Na/K pump

Co-Transport: When solute moves down its gradient (created by active transport process), it can go with another substance with it

Counter-Transport: When solute moves down its gradient (created by active transport process), it can be exchanged for another substance

Secondary Active Transport: Co-Transport

sodium-x Co-T where? 2

Others? ntk

Sodium-Glucose Co-Transporter

• Renal and intestinal epithelial cells

• Glucose transported into cell with Na+ once both molecules bind to receptor

• Glucose moves against gradient

• Na+ moves with gradient

• No ATP used!

More Ex

• with Na⁺: Amino Acids, Phosphate, iodine

• with others: K⁺, Cl^-, HCO₃^-, Fe, urate

Secondary Active Transport: Counter-Transport - aka

Na-X Con-T where?

Na-X Con-T where? weaker than?

aka exchanger

Sodium-Calcium Counter-Transport (NCX)

• Ca²⁺ is moving against its gradient

• Na⁺ is moving with its gradient

• cardiac > smooth muscles, neurons

Sodium-Hydrogen Counter-Transport (NHX)

• proximal tubule (PT) of kidneys (Na⁺ reabsorbed)

• Weaker vs ATP H⁺ transport in distal tubule (DT)

Action Potential: Outline

Membrane potentials

Diffusion potential

Equilibrium potential

Action potential

Refractory period

Anatomy of the neuron

Conduction types

Potential Difference

Membrane Potential

Resting Membrane Potential (RMP)

inside vs outside mV?

what else is highly negative inside the cell?

Potential Difference: Voltage difference b/w two points (Ohms Law)

Membrane Potential: Voltage difference across the plasma membrane (inside relative to outside)

Resting Membrane Potential (RMP): Voltage difference across the plasma membrane when cell is at rest

• Intracellular: -90 mV

• Extracellular: 0 mV

Charge inside of cell at (RMP) is negative

• Leaky K+ channels allow K+ to leave the cell down gradient

• High intracellular protein (protein is more negatively charged) concentration relative to extracellular concentration

Equilibrium Potential 2

Law of Electroneutrality 1

neutral vs balanced

Equilibrium Potential: The membrane potential that counters the chemical forces (concentration gradient) that would move an ion across the cell membrane, thus putting the ion in equilibrium

• Charge at which a specific ion will not move across membrane

• Equilibrium potential is not automatically 0 mV. Each ion has its own equilibrium potential based on its concentration gradient.

Law of Electroneutrality: the # of (+) & (-) charges must be equal across membrane

• Desire for the charge to be neutral across membrane

• This is more about ensuring that the charges are balanced more so than being perfectly neutral

• Ex: in acidosis H+ goes in and to keep balance, K+ must leave the cell

  • ↑ pH but hyperkalemia risk increases

Membrane Potential: Pump-Leak Model - 2

2 passive

1 active

• Na/K ATPase = ↑ Na+ outside & ↑ K+ inside

• Leaky Na+ & K+ channels allows each to flow down gradient

• K+ diffuses faster than Na+ = ionic asymmetry = more (+) charges leaving cell than entering cell = (-) membrane potential is created

• Resting Membrane Potential = -90 to -70 mV

  • Closest to Equilibrium Potential for most permeable ion (K+)

Equilibrium Potential (Nernst Potential) - define 1

Nernst equation

Membrane potential (voltage difference across cell membrane) at which a specific ion would be in "electrochemical equilibrium" - electrical & chemical forces are equal in force but opposite in direction

• resulting in No net movement of that specific ion in either direction across membrane

Calculated by Nernst equation, which considers the concentration gradient of the ion across membrane

• EMF (mV) = ±61 log (C_i / C_o)

• Considers the concentration gradient of the ion across the membrane

Equilibrium Potential of:

Na⁺

Cl^-

K⁺

Ca²⁺

Knowing this helps you see which direction the ions want to go

Action Potential

Resting Membrane Potential:

Depolarization:

Threshold Potential:

Action Potential:

Repolarization:

Hyperpolarizaton:

Resting Membrane Potential: voltage of cell at "rest"

Depolarization: cell b/c more positive compared to the RMP

Threshold Potential: voltage threshold a depolarization must reach to initiate an action potential

Action Potential: transient electrical impulse in which the membrane potential rapidly rises to a much more positive level than RMP

Repolarization: cell b/c more negative, returning to RMP

Hyperpolarizaton: cell b/c more negative, below RMP

• NaKATPase will fix this

Resting Membrane Potential - 2

maintained by?

Resting stage b/f action potential begins

Different for specific cell types (usually around –70 mV)

Membrane is said to be "polarized"

• Established by Na⁺/K⁺ pump

• Na⁺/K⁺ leak channels allow Na⁺/K⁺ to leak out of cell, even at rest

Depolarization - define

influx vs efflux

overshoot?

Membrane now permeable to Na+

Na+ & K+ channels open (K+ is very slow to peak)

Na+ influx occurs down its concentration gradient, bringing a positive charge inside axon

• Influx = movement into the cell

Polarized state is neutralized (depolarized)

Can "overshoot" above zero (positive charge)

Repolarization - 3

Na+ channels close & K+ channels takes over (peak)

Rapid K+ efflux down its concentration gradient, bringing a positive charge outside axon

• Efflux = movement out of the cell

Polarized state is restored

Voltage-Gated Sodium Channel

activation 2

inactivation 2 why?

Activation

• As MP rises (depolarizes), it reaches a threshold (-55 mV) that induces a conformational change

• Activation gate opens, allowing Na+ influx

• Na+ permeability increases 500- to 5000-fold

Inactivation

• Once +35 mV is reached the inactivation gate closes

• Na+ influx stops

• Inactivation gate remains closed until at or near RMP

  • Nerve can't depolarize again until repolarization has happened

  • Protective mechanism that prevents Na+ channels from reopening too quickly, and ensures that AP moves in one direction

Voltage-Gated Sodium Channel Visual

how many gates? aka?

gate movement as AP occurs 3

Activation Gate aka m gate (movement)

Inactivation Gate aka h gate (halt)

Voltage-Gated Potassium Channel

gates open when? why?

During Resting State

• Closed during resting state, preventing K+ ions from moving down their concentration gradient

During Action Potential

• When TP is met conformational change opens gate slowly and is fully open (peak) at about the same time VG-Na+ channels close at peak AP

• When EPP is met, BOTH channels are open!

  • K+ is slower than Na+

  • Na+ has an inactivation gate which K+ does not

Voltage-Gated Potassium Channel Visual

Activation Gate aka n gate (not yet)

Na+/K+ Conductance - define

Conductance means how easily ions can cross the membrane because their channels are open.

Na+ conductance increases several thousand–fold during the early stages of the action potential

K+ conductance increases only about 30-fold during the latter stages of the action potential and for a short period thereafter.

AP Summary - 2

Each AP = a sudden change from (-) membrane potential to a (+) potential and ends with (-) potential

Once MP reaches TP, an AP is created (all-or-none fashion) - can’t be stopped

Are rapid changes in membrane potential that spread rapidly along the nerve fiber membrane (like a domino effect)

To conduct nerve signal, the AP moves along nerve fiber until nerve terminal

Threshold Potential

too little vs too much stimulus?

A weak electrical stimulus may not be able to excite a fiber (subthreshold potential)

However, when the voltage of the stimulus is increased, there comes a point at which enough excitation occurs to elicit an action potential

This point is called a threshold potential (about –55 mV)

Note: The action potential does not get larger with a larger stimulus

Refractory Period - define

2 zones - exactly when it starts and end

what’s a greater stimulus?

Period during which the cell is incapable of eliciting a normal action potential d/t inactivated Na+ channels being closed

Absolute

• From initiation of action potential until membrane potential falls back below threshold potential

• Na+ channel h gate is closed until open = start of next zone

• No matter how great the stimulus, it is impossible to elicit another AP

Relative

• Begins just after absolute refractory period, when membrane potential falls below TP

• Lasts until membrane potential is reset to RMP

• some h gates reopened, but K⁺ conductance remains high → greater stimulus required to reach TP

  • Doesn’t change TP of -55 mV, you just need more ligands, more nGpcr, more ions compared to resting state

Re-Establishing Na+ & K+ Gradients

1 active vs 2 passive

what ions are missing? where?

• Na+ and K+ concentration differences are re-established by the Na+/K+ pump, essentially "recharging" the nerve for another AP

• When one gradient gets too much, then that is when the Na+/K+ leak channels start to send overflow back to the other side

• Ca+ and Cl- are more in cardiac cells

The Neuron - define

direction of AP

NT made? transported where? how?

Neurons are excitable cells

Once AP gets to Axon it goes ONLY in one direction

Dendrites receive graded signals; the axon initial segment generates action potentials.

Neurotransmitters synthesized in the Soma (body) then packaged & transported ⇆ axon terminal via microtubules

Neuron Make up visual

Myelin Sheath - b/t? measurement?

PNS vs CNS ex names

Myelination = ↑ insulation = ↑ speed

More myelination = more speed

Sheath interrupted every 1-3 mm at Node of Ranvier

Peripheral Nervous System

• Schwann Cell

Central Nervous System

• Oligodendrocyte

Propagation of AP:

Continuous Conduction - 2

Continuous conduction: An AP spreads along the entire unmyelinated membrane by depolarizing each adjacent section in a ripple fashion.

normally moves forward because the membrane behind it is in refractory.

Action Potential:

Saltatory Conduction

where?

benefits? 2

Action potential only occurs at nodes of Ranvier (Myelinated nerve fibers)

Increased velocity

Energy conservation

Action Potential: Manipulation using K⁺ - 2

RMP directly correlates with serum K+ levels

• ↑ K+ = ↑ RMP (more positive)

• In hyperkalemia, it pushes RMP closer to threshold, too much it can cause your AP to get stuck in the absolute refractory period

  • h gate stays closed and won’t open

  • h gate does not open at threshold potential. It reopens when the membrane becomes sufficiently negative during repolarization

Action Potential: Manipulation using Ca²⁺ - 2

TP directly correlates with serum Ca²⁺ levels

• ↑ Ca²⁺ = ↑ TP (more positive)

  • Giving Ca chloride IVP can help increase the distance between the RMP and TP

  • where ↑ K⁺ decreases the distance

• ↓ Ca²⁺ = ↓ TP (more negative)