Physiology - Musculoskeletal Block Flashcards
What is Ohm’s law?
V = IR
(voltage = current * resistance)
What does the Nernst equation show?
The potential difference (the voltage) of a single ion type across a cell membrane is related to the ion type’s concentration gradient
(I.e. the voltage is determined by the concentration gradient)
What does the Goldman (GHK) equation show?
Each ion’s Nernst potential contribution to the Emembrane is proportional to the membrane’s permeability for that ion
True/False.
Em and membrane voltage can be thought of as equivalent terms.
True.
What electrolytes and/or other substances provide most of the charge found on the outside of the cell?
(I.e. what electrolytes are found in high concentrations in the extracellular fluids?)
Na+
Cl<span>-</span>
What electrolytes and/or other substances provide most of the charge found on the inside of the cell?
(I.e. what electrolytes are found in high concentrations in the intracellular fluids?)
K+
proteins
What is the main ion pump maintaining cellular voltages?
The Na-K pump
What are normal serum Na+ levels?
What are normal serum K+ levels?
140 mM (135 - 145 mM)
4.6 mM (3.6 - 5.5 mM)
How are Nernst potentials generated?
Diffusion of ions down their concentration gradients
(e.g. K+ leaves the cell –> the cell becomes slightly more negative)
What two gradients are being balanced to produce a single ion’s Nernst potential?
An electrical and a chemical gradient
(e.g. K+ flows out along its concentration gradient, leaving behind an electrical gradient which draws K+ into the cell)
How much of the K+ inside a cell or Na+ outside the cell needs to move for a large change to occur in voltages?
An infinitesimal amount
(concentrations remain fairly constant)
What is the Nernst equation for K+?
EK = 60log10 (Ko / Ki)
From where does the ‘60log10’ in the Nernst equation come?
(EK = 60log10 (Ko / Ki))
RT / ZF ln = ~60
- Gas constant * absolute temperature*
- /*
- valence * Faraday’s constant*
_______ potentials are solved for individual ion potentials.
The __________ equation allows us to compare all these potentials on a single membrane.
Nernst;
Goldman (GHK)
What is the most important factor determing Em (membrane voltage) under physiological conditions?
The ratio of PK to PNa
(P = permeability)
How can membrane potentials (Em) change?
Change the ratio of Na+ to K+ permeability
(remember, Na and K concentrations hardly change at all –> only infinitesimal amounts move across membranes at any one time)
All cells in the body have a __ resting potential (Em).
This means all our cells are more influenced by __ than __.
-
K+, Na+
What resting Em would you find in an erythrocyte?
What resting Em would you find in a neuron?
What resting Em would you find in a cardiac myocyte?
- 10 mV
- 70 mV
- 90 mV
What would the Em (membrane potential) be if the charge outside and inside were the same?
0
(no potential difference = no voltage)
When the Em moves in a negative direction away from resting membrane potential, it is:
When the Em moves in a positive direction towards zero and away from resting potential, it is:
When the Em moves in a positive direction away from zero (the cell is now positive inside), it is:
Hyperpolarizing;
depolarizing;
a reversal of membrane potential (it has already depolarized)
If significantly small currents pass through excitable cells, what response do they have?
Passive return to resting potential
(action potential threshold not met)
If significantly large currents pass through excitable cells, what response do they have?
Active response / depolarization / action potential
(threshold surpassed)
How does a stimulated neuron’s membrane potential decrease as a function of distance/time down the axon if the stimulation did not reach the action potential threshold?
And if it did reach the threshold?
It decays exponentially;
there is no decay whatsoever
If you use a probe to stimulate an axon midway down its length, in which direction will the potential travel?
Both directions
(towards the synapse and towards the soma)
True/False.
Action potentials allow for graded responses.
False.
They are all-or-none responses
Which moves faster, an action potential or a different electronic potential (a subthreshold or hyperpolarizing stimulation)?
Electronic potentials
(action potentials are slower but don’t lose any potential with distance)
The Nernst equation tells us that individual ions have their own voltage based on ___________ gradients.
The Goldman (GHK) equation tells us that the permeability and ___________ of these ions together can be used to determine the ___.
Concentration;
Nernst potentials,
Em (membrane potential)
If you increase the permeability of a membrane towards a particular ion, what will happen to the overall Em (membrane potential)?
It will shift towards the Nernst potential for that ion
All cellular membrane potentials (Ems) can be found between the Nernst potentials for what two ions?
Sodium_______________________________________
0____________________________________________
Potassium_____________________________________
What event triggers the changes in permeability to Na+ and K+ necessary for an action potential?
Membrane depolarization
Upon membrane depolarization reaching threshold in a neuron, what are the three changes in permeability that occur next (in order)?
Sodium activation
Sodium inactivation
Potassium activation
How can membrane depolarization be tightly controlled during an action potential?
Via voltage-gated channels
(ALL opened via membrane depolarization, but at different speeds –> first, Na+ activation, then Na+ inactivation, then K+ activation)
Membrane polarization causes what to occur first in an action potential?
Membrane polarization causes what to occur second and third in an action potential?
1. Na+ activation (depolarization)
2. Na+ inactivation (repolarization)
3. K+ activation (repolarization)
In an action potential, both Na+ and K+ channels will be opened.
Is there an inactivation of the Na+ channel?
Is there an inactivation of the K+ channel?
Yes;
no
In the resting state, are either of the activation or inactivation gates open on a sodium channel?
In the resting state, are either of the activation or inactivation gates open on a potassium channel?
Yes, the inactivation channel;
sort of - there is no inactivation gate
Describe how a sodium channel’s activation and inactivation gates act from resting potential through an action potential and back to resting.
Describe how a potassium channel’s activation and inactivation gates act from resting potential through an action potential and back to resting.
If a neuron’s threshold lowers (becomes more negative), what happens to its excitability?
It increases
What refractory period occurs when neuronal sodium channels first close?
What happens when they reset?
The absolute refractory period;
the relative refractory period
When does the absolute refractory period end?
When does the relative refractory period end?
When Na+ channels reset;
when K+ channels close
What umbrella term refers to diseases that result from defects in normal ion channel/gate function?
Channelopathies
What type of Na+ channel inactivation occurs during an action potential?
What type of Na+ channel inactivation occurs between action potentials in response to new baseline resting potentials (changes in threshold / excitability)?
Transient inactivation;
steady-state inactivation
Sodium channel gates open and close based off surrounding voltages.
How does steady-state inactivation of Na+ channels change threshold excitability?
Changes in baseline membrane resting potential (hyperpolarization or depolarization) can increase or decrease the number of inactivated sodium channels, thus changing a neuron’s excitability
If you slightly depolarize a neuron (not quite to threshold) and just hold it there, what effect does this have on sodium channels in the membrane?
More channels are activated
(just moving up the curved line a bit in the attached graph)
What three steps should one take in analyzing the effects of a change in ion concentration on membrane potentials?
(assuming one ion has changed)
- Calculate the change in Nernst potential
- Determine if the resting membrane potential has changed
- Determine the effects on action potentials
What ion’s Nernst potential is the primary factor affecting cell membrane potentials (Em)?
K+
What is the normal neuronal Nernst potential for Na+?
What will happen to this value in cases of hyponatremia?
(Use the Nernst equation)
+ 65 mV;
it will get closer and closer to zero
What happens to action potentials in cases of hyponatremia?
(in terms of size and duration)
They have shorter peaks and longer durations
(On the attached graph, imagine an action potential taking place. The peak will be shorter and shorter as the E<span>Na </span>becomes less and less)
True/False.
All voltage-gated sodium channels are triggered at the exact same voltages.
False.
There is a spectrum of easy-to-stimulate and difficult-to-stimulate channels
When is a neuron’s membrane more permeable to sodium?
When is a neuron’s membrane more permeable to potassium?
During depolarization in an action potential;
during repolarization and at rest
What happens to neuron excitability in cases of hypokalemia?
Why?
(NOTE: hypokalemia refers to decreasing extracellular K+)
They become hypoexcitable (less irritable);
the cell becomes hyperpolarized –> less sodium channels are open (left graph); although, there is a greater fraction of available sodium channels for recruitment to an action potential (right graph)
Which is more likely to affect resting membrane potential, changes in K+ or Na+?
(Assume equal changes in either)
K+
(plasma membranes are more affected by K+ than Na+)
What effect will hypernatremia have on a cell’s resting membrane potential?
What effect will this have on action potential peaks?
It will become more positive;
they increase;
Changes in ________ concentration will typically have more dramatic effects on action potential peaks.
Changes in ________ concentration will typically have more dramatic effects on resting membrane potentials.
Sodium;
potassium
As extracellular potassium levels increase, the EK moves towards or away from 0?
Towards
(as [Kout] / [Kin] approach 1, the equation below gets closer to the log of 1, which is 0)
Nernst equation = Ek = 60Log10 ([Kout] / [Kin])
Use the Nernst equation (see below, but try to write it yourself first) to answer the following questions:
1. What effect will hyperkalemia have on resting membrane potentials and cell excitability.
2. What effect will hypokalemia have on resting membrane potentials and cell excitability.
Nernst equation = Ek = 60Log10 ([Kout] / [Kin])
- Hyperkalemia = depolarization, more irritable
- Hypokalemia = hyperpolarization, less irritable
What is the normal neuronal Nernst potential for K+?
What will happen to this value in cases of hypokalemia?
(Use the Nernst equation)
-80 mV;
it will become more negative (hyperpolarize)
What is the normal neuronal Nernst potential for K+?
What will happen to this value in cases of hyperkalemia?
(Use the Nernst equation)
-80 mV;
it will become less negative (depolarize)
True/False.
Changing the resting membrane potential for any cell will affect the steady state Na+ channel curves for that cell.
(Attached below)
True.
Which are more important, effects of activation or inactivation in steady-state Na+ channel control?
(Curves shown below)
Activation
As a neuron’s threshold increases, excitability _________.
Decreases
As a neuron’s threshold decreases, excitability _________.
Increases
Explain why increasing amounts of extracellular K+ will cause increases in neuronal excitability up until a certain point where the increasing K+ inactivates the neurons.
(See image below)
First, more sodium channels are activated by the cell membrane depolarization;
at a certain point, too few channels remain available for recuitment to an action potential
What effect does ischemia have on cell ion channels?
(Especially relevant in neurons)
What is the effect on Nernst potentials and Em?
Non-specific leak of all ions;
Nernst potentials and Em all approach 0
- (sodium channels are inactivated, depolarizing blockade)*
- (in addition, no energy is available to re-pump the ions to their correct concentrations)*
Why does increasing extracellular potassium eventually result in smaller and smaller action potential peaks?
The cell’s resting membrane potential depolarizes more and more and so less and less sodium channels are available
(graph on right)
True/False.
The amount of Ca2+ entering the nerve terminal is not related to the amount of neurotransmitter that is released.
False.
The more Ca2+ entering the terminal, the more product released into the synapse.
What effect does increasing extracellular calcium have on excitable cell excitability?
Why/how?
It will decrease excitability;
it hinders flow through Na+ channels
(Note: in some cells, Ca2+ also opens calcium-gated K+ channels)
Action potentials in the SA and AV nodes are exclusively dependent on what ion?
Ca2+
The depolarization and plateau phases (phases 0 and 2) of ventricular action potentials are dependent on what ions?
Sodium and calcium
Besides protection, what are the main functions of glial cells in terms of the extracellular neuronal environment?
Regulating:
[K+],
glutamate,
osmolytes,
etc.
Why is it so important that glial cells tightly control extracellular K+ concentrations?
Why is it so important that glial cells tightly control extracellular glutamate?
To prevent increased cell depolarization and excitability;
same reason
What would the value of Em be if the permeability of the cell membrane to Na+ was increased, such that PK = PNa?
Em = -15 mV
(If PK = PNa, the new Em lies halfway between EK and ENa)
What’s the difference between an electrical synapse and a chemical synapse?
Electrical - gap junction flow
Chemical - neurotransmitter diffusion
How does calcium get into nerve terminals to trigger neurotransmitter release?
How does it get back out?
An action potential comes down the axon and triggers voltage-gated calcium channels;
sodium-calcium exchangers, ATPase pumps
What are some methods by which neurotransmitter is removed from the synaptic cleft?
Reuptake;
catabolism;
diffusion;
glial cell uptake
What is unique about the structure of the axon in the neuromuscular junction?
What unique effect does this provide?
It ends in many synaptic boutons (all on one single myocyte per axon);
more neurotransmitter is released (and faster) in these synapses than any other
Different neurotransmitters can have different effects depending on the tissue receptor on which they are acting.
For example acetylcholine is stimulatory to ___________ and inhibitory to ___________ receptors.
Nicotinic;
muscarinic
What drug blocks muscarinic receptors?
What drug blocks nicotinic receptors?
Atropine;
curare
One axon can synapse on how many myocytes?
Only one
Why is so much neurotransmitter needed at the neuromuscular junction?
To go way, way above the myocyte threshold and ALWAYS produce the desired response
(you don’t want your muscles to only sometimes fire when you ask)
In which direction do EPSPs drive the membrane potential?
Towards (or past) threshold
In which direction do IPSPs drive the membrane potential?
Away from threshold (usually hyperpolarizing)
An excitatory post-synaptic potential (EPSP) usually has a membrane potential of about what?
An inhibitory post-synaptic potential (IPSP) usually has a membrane potential of about what?
Well above threshold (typically - 5 to - 10 mV);
below threshold (often similar to EK)
(it can even be above the resting membrane potential and depolarize the cell a bit; however, if it’s potential is below threshold, it’s inhibitory)
Where is the highest concentration of voltage-gated sodium channels in the neuron?
The axon hillock
True/False.
EPSPs and IPSPs sum in a quasi-algebraic manner.
True.
The amount of neurotransmitter released from the axon terminal is directly proportional to:
The amount of calcium entering the axon terminal
Do the antibodies in myasthenia gravis destroy, downregulate, or just inactivate acetylcholine-gated sodium channels?
Likely all three
(inactivation and destruction and downregulation)
What is the penumbra of a stroke?
What change in membrane potential (Em) do cells in the infarcted area undergo?
What change in membrane potential (Em) do the penumbra cells undergo?
Affected tissues that are not as ischemic as the core area of the stroke;
membrane potentials dissipate (to 0 mV);
there is no large change in membrane potentials in the penumbra
What leads to the ‘latched state’ in smooth muscle?
Dephosphorylation of myosin light-chain
Via what intracellular effect does beta-adrenergic stimulation cause smooth muscle relaxation in the bronchi?
Increased cAMP
Growth hormone acts especially on which layer of cartilage in endochondral ossification?
The reserve cartilage
How does colchicine stabilize microtubules and inhibit synthesis?
By binding/sequestering tubulin dimers
What drug inhibits interactions between leukocyte integrins and endothelial cells?
This stops T cell extravasation and may be beneficial in what disease?
Natalizumab;
multiple sclerosis
Which of the following may be beneficial in treating lysosomal storage disorders:
Macromolecule dietary restrictions
Bone marrow transplant
Substrate inhibition therapy
Enzyme replacement therapy
Bone marrow transplant
Substrate inhibition therapy
Enzyme replacement therapy
(NOT macromolecule dietary restrictions)
What can be given to athletes in long-term events (e.g. marathons) to slow down glycogenolysis in the liver?
Oral glucose
How does repetitive nerve activity lead to short-term enhancement of neurotransmitter release?
Ca2+ accumulates in the nerve terminal
