Week 1 Flashcards
What is the cell membrane composed of?
Phospholipid bilayer
What easily diffuses through the membrane?
Lipid soluble molecules and gases
What cannot cross the membrane without help?
Water soluble molecules
What is the membrane impermeable to?
Organic anions (proteins)
What does permeability depend on?
Molecular size, lipid solubility, and charge
What do polar molecules and ions need to help of while crossing the membrane?
Protein carriers or channels
Simple diffusion
Small, lipid-soluble molecules and gases pass either directly through the phospholipid bilayer or pores down the concentration gradient. It involves the Brownian motion. It is a passive process.
Carrier proteins
They aid the movement of polar molecules (sugars and amino acids) across cell membranes. they are NOT continuous pores in the membrane.
Facilitated diffusion
It is a passive process in which molecules diffuse across a membrane with the assistance of a carrier protein down the concentration gradient.
when does the system of facilitated diffusion get saturated?
If the number of molecules exceeds the number of transporter proteins, the system gets saturated.
Primary active transport
It is a mechanism to move selected molecules across cell membranes against their concentration using energy from ATP hydrolysis.
There is a conformational change in the carrier protein.
Secondary active transport
When a substance is carried up its concentration gradient without ATP catabolism, it is known as secondary active transport.
Channels
Membrane-spanning protein forms a ‘pore’ right through the membrane. 4-5 protein subunits fit together such that the pore can be created. it also has a pore loops.
how is secondary active transport powered?
The kinetic energy of movement of one substance down its conc gradient powers the simultaneous transport of another up its conc gradient.
What do the physical properties of the pore loop create?
Selectivity filter
Gated channels
Channels can be closed off by a branch of a protein structure which functions as a ‘gate’
factors determining channel protein shape
Ligand-gated channels: binding of a chemical agent
Voltage-gated channels: voltage across a membrane
Ligand-gated channels
The binding of a receptor with its ligand usually triggers events at the membrane, such as the activation of an enzyme.
What do cell membrane receptors play an important role in?
Synaptic transmission
Voltage-gated channels
They are sensitive to the potential difference across the membrane (eg. depolarization), and change the conformation of the channel subunits causing a diffusion pore to be created.
where is the voltage sensing mechanism in a voltage-gated channel located?
4th transmembrane domain of the protein, the S4 segment
Explain the positions of the S4 wings
The natural position is up towards the outer surface of the cell membrane. but when the membrane is polarized, the positively charged wing is attracted downwards to the negatively charged inner surface of the membrane.
What happens after depolarization of the membrane to about -50mV?
It no longer provides sufficient electrical attraction to hold the S4 wing downwards. In the up position, S4 removes a structural occlusion from the pore such that ions can now diffuse through it.
Endocytosis
inward pinching of a membrane to create a vesicle, usually receptor-mediated to capture proteins from outside to inside.
Exocytosis
Partial or complete fusion of vesicles with cell membrane for bulk trans-membrane transport of specific molecules, from inside to outside.
2 types of exocytosis
- kiss and run
- full exocytosis
Kiss and run
- The secretory vesicles dock and fuse with the plasma membrane at specific locations called ‘fusion pores’
- vesicles connect and disconnect multiple times before contents are emptied
what are diffused contents from vesicles into interstitial fluid used for?
low rate signalling
Full exocytosis
complete fusion of the vesicle with the membrane, leading to total release of contents all at once.
What is full exocytosis necessary for?
delivery of membrane proteins and high levels of signaling
what is full exocytosis counterbalanced by?
endocytosis to stabilize membrane surface area
what do vesicles in full exocytosis carry?
it can carry neurotransmitters released all at once or it can involve membrane-bound proteins (receptors, ion channels) destined to be part of the membrane.
2 conditions to generate membrane potential
- 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.
Na+/K+ dependent ATPase
the enzyme that moves Na+ out of the cell and K+ into the cell by breaking down ATP
Na+/K+ pump main mechanism
3Na+ ions are pumped out and 2 K+ ions are pumped in creating a conc gradient
how much energy does the Na+/K+ pump consume
1/3 of the energy needs of the body (2/3 of neurons)
Resting membrane potential
-70 mV, due to being very permeable to K+.
K+ diffuses out of the cell through the K+ leak channels, hence cations accumulate outside, making it net negative inside.
What does the Na/K inequality create
Potential difference of -10mV (more negative inside the membrane with respect to outside)
How can membrane potential be calculated?
nernst equation - it describes the balance between chemical work of diffusion and with electric work of repulsion
When do we reach the equilibrium state?
The efflux of K+ occurs until there is such a build up of K+ on the outside of the membrane that the further diffusion of K+ is repelled by electromagnetic force
Equilibrium potential if only K+ is involved
-90 mV
why is membrane potential -70mV and not -90mV?
Membrane is most permeable to K+ at rest, but Na+ and Cl- ions are also diffusing
Goldman equation
Expanded Nernst equation. The Em can be calculated through it
What happens to Cl- ions inside the cell?
inside the cell there are large proteins (they are trapped, and can only get outside using exocitosis). hence cl- gets more conc on the outside.
Na+ equilibrium potential
sometimes, permeability of Na+ can be dominant and much more than K+, then there net Na+ current inwards
why do cl- get more conc on the outside in the extracellular space?
due to anion proteins oresent on the inside and not due to the active pump.
how are signals generated?
Membrane increases its conductance by opening a channel permeable only to the Na+ ion - voltage gated Na+ channel.
the membrane needs to be depolarised to open the Na+ channel
What is needed for the Na+ voltage gated channel to open?
the threshold potential (-55mV) needs to be reached by depolarization
How does Na+ channel inactivation take play?
ball and chain inactivation gate closed half a second after the activation gate opens. this is at +30 mV.
Action potential
An impulse, a very short-lived change in the MP, its used as a signal
Where can APs in a membrane be produced?
only in membranes that contain the voltage gated Na+ channels . the presence of these channels make the membrane excitable.
Threshold potential
Minimum depolarization is needed to induce the regenerative mechanism for opening Na+ channels to generate an AP
All or none principle
threshold and supra-threshold stimuli generate the same magnitudee
frequency coding
Information. pertaining to stimulus intensity is coded by the changes in frequency of AP
refarctory period
period after Ap where all Na+ channels are inactivated. they remain inactivated until threshold is reached again
absolute rp
none of the channels are reconfisgured
relative rp
some but not all channels are reconfigured
depolarization block
complete blockage of ap producction by keeping the membrane depolarized (around 20mV)
OR
destroy the conc gradient for K+, by introducing more K+ in the extracellular space. this will result in permanent Na+ inactivation and the membrane will remain in absolute Rp and becomes in-excitable.
aafter hyperpolarixation
the presence of K+ channels, in conjunction with the K+ leak channels will cause a much greater outward K+ current, causing the mp to be more polarized than normal (-80mV)
What does the local reversal of potential difference from -70 mV to +30 mV do?
It serves as the source of depolarizing current for the adjacent membrane.
what do the un-excitable cells do?
they conduct passive currents but cannot generate APs
Axon
long extension of the cekk body that carries AP to another location
Synapse
the reguion where an axon terminal communicates with its postsynaptic target cell
Membrane as a circuit
presence of resistors and capacitors. we can see that there is a loss in amplitude because of low electricity conductance
length constant (lambda)
it measures how quickly a potential difference disappears (decays to 0) as a function of distance –> where the voltage drops to about 37% of its original value
What the conduction velocity of an AP across an axon depend on?
length constant
2 mechanisms involved in the nervous system to improve
- The length constant is increased by increasing the axon diameter. (The larger the diameter, the larger the internal resistance: less voltage is lost
- The length constant is increased by increasing membrane resistance (the higher the membrane resistance, the less current gets leaked out: currents get forced out of the membrane)
3 factors length constant is defined with
internal; resistance, extracellular fluid resistance and membrane resistance
How to increase membrane resistance?
Myelination
Glial cells
they assist the nervous system and are required for nutrition and increased membrane resistance by reducing leakage of current outside the membrane.
there are small gaps between the wrapping of the glial cells.
specialized glial cells
Schwann cells of PNS or oligodendrocytes of CNS
schwann cells
wrap around a single portion of the one axon (cytoplasm all squeezed out)
oligodendrocyte
they have a number of processes that streak out and wrap a whole bunch of axons individually
multiple sclerosis (MS)
Disease caised due to a damaged myeling sheath.
it causes the blockage of messages , pins and needles and memory problems
Node of ranvier
small gaps left by adjacent glial cells
Saltatory conduction
Jumping from one NOR to another
if we an AP on one node and the depolarizing current is strong enough it gets transferred down 5-10 nodes bringing them to threshold potential
furthest node - 10th node - serves as the depolarizing force for the next 10 nodes
Electrical synapse
at electronic synapses (gap junctions) adjacent members are about 35 A apart, the gap junctions are bridges by connexions which allow small ions (and depolarization) to cross
seen in cardiac muscles
Unmyelinated axons
they have some insulation: the schwann cells and oligodendrocytes engulf the axon without winding - Remak bundle
chemical synapse
here neurotransmitters are released in the extracellular space present between cells. the synaose is defined by the presynaptic surface (bouton) and the postsynaptic membrane
synaptic cleft
space between the two neuronal cells
the space is specialized due to the existence of a postsynaptic membrane which contains specific protein receptors that will bind that transmitter molecule after it is released
axon terminal
they end in boutons filled with vesicles
neurotransmitter release from vesickes
- bouton membrane containing Ca2+ channels open when depolarized by AP currents to -50mV
- Ca2+ diffuses into bouton and triggers a cascade of tractions which result in exocytosis
chance of vesicle release
it is probabilistic - 10-90% chance of releasing 1 vesicle
