Lectures 2-3 : Resting Membrane & Action Potential Flashcards
what is important about the phospholipid bilayer?
has hydrophilic heads with hydrophobic tails → does not allow most ions through except using proteins and ion channels
why is water important?
- water is the main ingredient in the intra and extracellular fluid
- water is a polar solvent so molecules like NaCl will separate
what are ions and why are they important?
- molecules that have a net electric charge
- insulated by spheres of hydration
- charge is determined by difference between protons and electrons
what are proteins made of?
- sequences of amino acids (connectivity is determined by R group)
how do ions diffuse across the cell membrane?
- protein channels span the cell membrane, and are made up of several subunits which form a pore
what are the states of the ion channels?
open & closed
what parts of the protein pore is hydrophilic vs hydrophobic?
parts that contact extracellular fluid and cytosol = hydrophilic
parts that span membrane = hydrophobic
what are the 2 important properties of a pore?
- selectivity = the size and charge of the pore determines the ions
- gating = many ion channels can open or close based on the microenvironment (can open in response to ligand binding or change in voltage)
what does resting membrane potential depend on?
- relative ion concentrations inside and outside of the cell
what are the ion concentrations in axoplasm and extracellular fluid?
how are ion concentration gradients established and maintained?
- sodium-potassium pump
- 3 Na out / 2K in
- runs constantly at constant rate
what is important about pump?
- moves ion against their gradients
- takes up 30% of all ATP and 70% of brain ATP
what does the calcium pump do?
- transports Ca out of cytosol into extracellular fluid
(important for synaptic transmission) - pumps Ca ++ into organelles like mitochondria
what are the two membrane forces?
diffusion/ gradient
- molecules prefer to move from an area of high to low concentration
- this process requires an open channel for the ion to move/diffuse through
electricity
- electrical current = conductance x electrical potential
what do you need for an ion to move across the channel?
- open channel for the membrane to cross
- a difference in the electrical potential across the membrane
what does Vm represent?
the charge of the inside of the membrane in comparison to the outside
when is equilibrium reached?
diffusion force = electrical force
equilibrium potential sign meanings?
pos = move in
neg = move out
what is the reality of asymmetrical charges?
- the asymmetry in the number of ions on the two sides of the membrane involves a small percentage of all ions
driving force formula?
what happens to driving force when Vm = Eion
positive vs. negative driving force?
pos = ions pushed out of cell
neg = ions pushed into cell
driving forces of k and na (neg, 0, pos)?
how is Eion predicted?
Nernst equation
out/in
what happens when ion in is greater than ion out?
fraction is greater than 1 = neg Eion
what happens when ion out is greater than ion in?
fraction is less than 1 = pos Eion
how can u calculate membrane potential?
GHK formula
- based on the relative concentration gradients
- dependent of permeability of an out/in
Ohms Law?
current = (conductance) (Vm)
voltage = (current) (resistance)
current formula?
current = (driving force) (contuctance)
driving force meaning?
energy pushing ions in or out of cell
ionic conductance meaning?
the capability of an ion to cross a membrane
ionic current meaning?
ion movement across membrane
what is a k+ mutation?
Weaver mice
- K+ channel mutation, allows the channel to pass both K+ and
Na
- Because of increased Na+ permeability, resting potential is more positive than normal and neuron function is compromised
- Called Weaver, because the mutation causes abnormal posture and movement, they die pre-maturley
what is the purpose of an action potential?
- encode all information in the nervous system
what is an action potential?
a rapid increase in membrane potential
= depolarization of the cell
- all or nothing
- important for information transfer between neurons
why do they occur?
- axons are long
- axoplasm is a poor conductor
- axons are leaky
what are the phases of an action potential
when is the membrane negative vs. positive in an action potential
what is the action potential threshold?
-40 mV
what happens when one steps on a thumbtack?
1) sensory input
2) physical energy leads to change in Vm
what determines AP firing rate?
- degree of depolarization
how is information coded?
- in firing rate
- different parts of the brain respond to different sensory inputs, memories, emotions etc
(even within a brain area, different cells respond with greater or fewer action potentials to different inputs)
what are the 4 channels involved in an action potential?
1) K leak
2) K voltage
3) Na voltage
what is K leak channel responsible for?
- how close Vm
(how it is 40x more permeable to Na and Vm is closer to Ek)
what are the 2 things that are always happening in the cell?
- Na/K pump
- K leak channel
where are Nav and Kv channels located?
in the axon membranes
where are the most Na voltage channels located on neuron?
Axon Hillock
what is the NaV channel?
a pore in the membrane that is highly selective for Na+ and dependent on changes in the membrane voltage
ball and chain
ball chain steps and corelation with AP?
1) open with little delay when Vm reaches threshold (activation)
2) they stay open for about 1 msec and then close b/c ball swings over opening (inactivation)
3) they cannot be open again until Vm is below -65 in undershoot phase (deinactivation)
4) channels can open again
Kv channels steps?
1) Open in response to depolarization
but only 1 msec later (not
immediately like VG Na+ Channels)
2) Opening of VG K+ Channels → K+
flows down concentration gradient and outside the cell → hyperpolarization (counteract depolarization of AP in order to repolarize neurons i.e. return peak membrane potential towards negative resting Vm)
what are the 2 ways that threshold can be reached?
1) transduction
2) signaling from NT
Resting state steps?
Passive Depolarization?›
Rising phase?
Overshoot?
Falling phase?
Undershoot?
Absolute and relative refractory periods?
Rare diseases due to ion channel mutations? (3)
Generalized epilepsy with febrile seizures
– seizures start in early childhood
– Na+ channel mutations
– slow Nav inactivation -> neurons are hyperexcitable
Benign familial neonatal convulsion
– frequent brief seizures
– K+ channel mutations
– reduced K+ current in AP falling phase -> neurons are
Episodic ataxia
– episodes of poor coordination of movement and balance (ataxia)
– various K+ channel mutations impair AP repolarization
Ion channel toxins 2
Tetrodatoxin (TTX)
* puffer fish (“fugu”) ovaries, liver, intestines (from ingested bacteria)
* 23 people have died since 2000 in Japan from fugu consumption
* x1200 more toxic than cyanide and no antidote
* blocks Na+ channels and stops action potentials (1mg is lethal)
* muscle paralysis -> asphyxiation
Saxitoxin (STX)
* poisoned by eating shell fish that have ingested
dinoflaggelates (algae)
* x100 more lethal than sarin nerve gas
* CIA suicide pills
* also blocks Na+ channels and action potentials
Local anesthetics?
- locally block APs
- cocain - lidocain
- block Na+ channels
- APs in small axons are affected most
- most pain nerves are small
how do APs affect other neurons?
- the AP must propagate to the axon terminal and synapses
- inflow of Na+ ions will depolarize neighboring patches of membrane to threshold
- propagation is one way due to refractory period
more current flow down — axons
wider
larger axons conduct APs —
faster
what are the two paths that positive charge can take?
- inside axon
- across axonal membrane
relationship with 2 axon pathways?
increase diameter - more current down axon
fewer open membrane pores - more current down axon
MS facts?
degrades mylein, disrupting AP conduction
targets oliodengrolia CNS
women are 2-3 times more likely to have MS
affects .02% of general population
siblings 5% - identical twins 31%
environmental factors
- temp, climate, low vitamin D, smoking
MS symptoms?
- numbness
- weakness
- electric shock sensations
- fatigue
- blurred vision
