PSL Membrane Notes PDF

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Physiology - OctoberMembraneLesson 1Cell Membrane✽ Membrane Overview○ The cell membrane is not an inert bag holding the cell together ○ Cell membrane = composed of Phospholipid bilayer ○ Lipid-soluble molecules and gases diffuse through readily ○ Water-soluble molecules cannot cross without help ○ I...

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Physiology - October

Membrane Lesson 1

Cell Membrane ✽ Membrane Overview ○

The cell membrane is not an inert bag holding the cell together

○

Cell membrane = composed of Phospholipid bilayer

○

Lipid-soluble molecules and gases diffuse through readily

○

Water-soluble molecules cannot cross without help

○

Impermeable to organic anions (proteins)

○

Permeability depends on molecular size, lipid solubility, and charge

✽ Membrane Permeability ○

If a substance can cross the membrane by any means, the membrane is permeable to that substance

○

Gases can diffuse across the membrane

○

Polar molecules and ions need the help of proteins (channels or carriers) to cross

✽ Simple Diffusion ○

Simple Diffusion: Small, lipid-soluble molecules and gases (e.g. O2, CO2, ethanol, urea etc...) pass either directly through the phospholipid bilayer or through pores

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Movement of substance is down its [ ] gradient

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The relative rate of diffusion is roughly proportional to the [ ]

○

Passive: No energy input required from ATP

gradient across the membrane

✽ Facillitated Diffusion ○

Facilitated Diffusion is a process of diffusion, where

molecules

diffuse

across

the

membrane, with the assistance of carrier protein ○

Carrier protein aid the movement of polar molecules (e.g. sugars and amino acids)

○

across the cell membrane Movement of substance is down its [ ]

○

The energy comes from the [ ] gradient of the

○

Passive: No energy input required from ATP

○

What if we want to move molecules against its [ ] gradient?

gradient solute

✽ Active Transport

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Active Transport is a mechanism to move selected molecules across cell membranes, against their [ ] gradient

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Substance binds to a protein carrier that changes conformation to move substance across a membrane

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Active Requires energy from ATP hydrolysis

○

ATPases(Na+/K+ Pump)

Channels

1. Mem󰇼󰈹󰈀n󰇵 C󰈊a󰈞n󰈩󰈗󰈼 -

Membrane spanning protein forms a ‘pore’ right through the membrane -4-5 protein subunits fit together such that a central pore is created through membrane, through which specific ions can diffuse through

-

These ‘Pore loops’ of the protein molecules dangle inside the channel

-

Physical properties of the pore loops create a selectivity filter

-

electric charge) These ‘pores’ are called Membrane Channels

-Only specific molecules can diffuse through (by means of size and

2. Gat󰈩󰇷 󰉑󰈋󰇽n󰈝e󰈘s -

Membrane channels generally are not kept perpetually open

-

Channels can be closed off by a branch of the protein structure that functions as ‘Gate’

-

Under certain conditions, the gate is closed, and no diffusion takes place, under other conditions the gate is open and diffusion is allowed (remember that it is still selective)

-

The protein components switch between 2 shapes; one creates an open pore, the

-

other blocks the pore Factors determining channel protein shape: - Ligand gated channels: Binding of chemical agent - Voltage gated channels: Voltage across the membrane

A. Lig󰈀󰈝󰇶 G󰇽te󰇷 󰉑󰈋󰈀n󰈝󰇵󰈘s -

Cell membrane receptors are part of the body’s

-

The binding of a receptor with its ligand usually such as activation of an enzyme

B. Vol󰉃󰈀󰈈󰇵-Gat󰈩󰇷 󰉑󰈋󰇽n󰈝e󰈘s -

Some membrane channels are sensitive to the across the membrane (e.g. depolarization), conformation of the channel subunits causing a diffusion pore to be created

-

The voltage sensing mechanism is in the 4th transmembrane the S4 segment

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S4 sticks out to the side of the protein (like a wing)

-

The natural position of the S4 ‘wing’ is up towards the outer membrane. But when the membrane is polarized, the positively attracted downwards to the negatively charged inner surface of

-

Depolarization of the membrane to about -50 mV no longer electrical attraction to hold the S4 wing downwards, so it migrates

-

In the up position, S4 removes a structural occlusion from the pore ions can now diffuse through it

Endo/Exocytosis Endocytosis

Exocytosis

inward ‘pinching’ of the membrane to create a vesicle; usually

partial or complete fusion of vesicles with cell membrane for bulk

receptor-mediated to capture

trans-membrane transport of specific

proteins, from outside to inside.

molecules, from inside to outside.

Exocytosis -

Intracellular materials, packaged in vesicles, are either secreted or delivered to the plasma membrane by exocytosis

-

There are 2 different types of exocytosis, with different docking mechanisms -

Exocytosis 1: The more rapid mechanism has been dubbed the ‘Kiss and Run’ -

Kiss and Run: The secretory vesicles dock and fuse with the plasma membrane at specific locations called ‘fusion pores’

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The vesicle can connect and disconnect several times before contents are emptied

-

Since only part of the contents are emptied in one ‘Kiss’, the process can be repeated several times before the vesicle is depleted

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Generally only part of vesicle contents diffuse into the interstitial fluid, used for the low rate of signalling

-

Exocytosis 2: Full exocytosis -

Full exocytosis: This involves complete fusion of the vesicle with the membrane, leading to the total release of vesicle contents at once

-

Necessary for delivery of membrane proteins and high levels of signalling

-

Must be counterbalanced by endocytosis to stabilize membrane surface area

Membrane Potential ○ ○

All cells in the body generate Membrane Potential (MP) To generate MP we need 2 conditions: -

Create a concentration gradient: an enzyme ion pump (functions as an ATPase) must actively transport certain ion

species

across

the

membrane

to

create

a

concentration gradient ○

Semi-permeable membrane: allows one ion species to

diffuse across the membrane more than others Diffusion of that ion species down its conc. gradient creates an electrical gradient

Na+/K+ Pump ●

All cell membrane is loaded with Na+/K+ pumps, this is the staple of all living

●

Na+/K+ dependent ATPase is an enzyme that moves Na+ out of the cell, and

●

K+ into the cell by breaking down ATP For each ATP molecule broken down, 3 Na+ ions are pumped out and 2 K+

cells.

pumped in (creates a concentration gradient)

●

Consumes 1/3 of energy needs of the body (in neurons it’s 2/3, i.e. huge consumer of energy)

●

Na/K inequality > potential difference of -10 mV

Resting Membrane Potential ○

So is our resting MP roughly -10 mV?

○

No! the actual resting MP in neurons is not -10mV but it’s closer to -70 mV, why?

○

Since our Resting MP is closer to -70 mV, something else is obviously happening > this is due to diffusion of K+ ions outwards

○ ○

The ‘resting’ membrane is most permeable to K+ ion K+ diffuses out of the cell, down the concentration gradient, via

○

Cations accumulate on the outside of the membrane, leaving net

○

This efflux will occur until

K+ channels negativity inside the membrane there is such a build-up of “+” charge on the outside of the membrane that further diffusion of K+ is repelled by the electromagnetic force = i.e. we reach an equilibrium situation

Equilibruim Potential ○

At equilibrium, electrical work to repel outward cation diffusion

○

Membrane potential at equilibrium is determined by the concentration gradient

○

Can be calculated using the Nernst Equation

equals chemical work of diffusion down conc. gradient

Resting Membrane Potential ●

In the ideal situation, the Nernst equation describes the balance between the chemical work of diffusion with electrical work of repulsion

●

The equation gives the potential difference across the membrane, inside with

●

The result is valid if and only if one ion species (K+ in this case) is diffusing

respect to outside, at equilibrium across the membrane

K+ Equilibrium Potential ○

If you calculate using the K+ ion you get: EK+ = (RT/F) ln([K+]o /[K+]i) = -90 mV (equilibrium potential for K+)

○

This is what the MP would be if only K+ ions was involved

○

But in the typical neuron, the resting MP is NOT -90mV, it’s about

○

What’s happening?

-70 to -80 mV...