Second Half Lecture Notes Flashcards
Neurophysiology
the study of structure and function in the nervous system
In order to maintain homeostasis
You need to be able to detect gradients in homeostatic parameters. You also need to know whether those gradients are driving significant exchanges that are going to drive bodily conditions outside of homeostatic limits to make responses.
The environment
- There is external environment: this is gradients
- there is internal environment we have to be worried about this environment in terms of regulating conditions in relation to homeostatic parameters
Stimuli
“information”
in the form of some sort of energy: heat, light, pressure of wind. These can also be concentration gradients
The first part of the nervous system
Receptors. These receive stimuli. Can either be a part of the nervous system or embryologically derived from different parts of the nervous system.
What is the responsibility of the receptors?
To convert energy from the stimuli into a source of energy that the nervous system can actually use.
Two key things about receptors
- they are very selective
- when we say that they convert energy into something that we can use, we say they are functioning as a transducer. The receptors are very limited in what can be transduced– for example you eyes can’t transduce the same information that ears can. Pressure sensors can’t transduce heat or cold.
What happens after information has been transduced?
The information is sent to some sort of decider. We usually think of this as the brain but that is not always the case.
What does the decider do?
It processes information and makes decisions.
What’s another example of something that can act as a decider?
The spinal cord. For example when you step on something sharp, you will pull your foot away immediately because the spinal cord reacts before the brain
What happens when the decider decides to do something?
It will issue instructions that are sent to the appropriate effectors.
What are the effectors?
Organ systems in the body that are going to bring about whatever response is necessary; piloerection, etc.
action potential
the information flow sent from the receptors is sent in the form of an action potential. Receptors change energy contained in stimuli to action potentials. Instructions are sent via action potential, responses require action potentials, and basically every movement and regulation requires action potentials.
Polyspermy
when two sperm bind to the egg and fertilize it
How is polyspermy prevented?
when one sperm fuses, an action potential occurs and doesn’t allow any more sperm to bind to the egg
neuron
cell type that gives most of the functional properties to the nervous system. They convey instructions and do the processes and sometimes the effector.
Typical neuron
the neuron that is in your spinal cord and generally the type of neuron that controls your skeletal muscles.
soma
the part of the neuron that contains DNA
dendritic zone
contains the dendrites that surround/come out of the soma
axon
hollow tube of cytoplasm that comes off the soma. can carry a signal from your spinal cord all the way to your big toe
Telodendrion
branches of the axon. Each of these telodendrions terminate in bulbs called synaptic bulbs.
Membrane potentials
resting membrane potential and action potential
resting membrane potential
exhibited by every cell and in every organism when it’s alive
action potentials
lots of cells cannot generate action potentials
excitable cells
cannot generate an action potential
What accounts for potential?
The difference in charge on the inside and outside of cells.
ion concentrations in a cell
Usually you will find a high concentration of K+ inside the cell and a high concentration of Na+ outside of the cell
How is the gradient of Na+ to K+ maintained?
By an ATPase sodium pump. A neuron will spend about 50% of its daily energy on maintaining gradients.
What causes the negative charge inside the cell?
Non-diffusable anions. They cannot move through the PM at all. Ex: amino acids, proteins. They get paired with a K+ and get stuck in the membrane and don’t diffuse with potassium.
What determines the magnitude of membrane potential?
the rate of K+ eflux. 30K+ will move with every one Na+
Current
the flow of charge. almost never considered as electron movement. instead it is the ionic current: K+, Na+, Cl-
depolarization
potential has gotten smaller (compared to resting)
hyperpolarization
potential has gotten bigger (compared to resting)
repolarized
when the membrane potential returns to resting
Electric charge
- Charge is a fundamental property of matter.
- Charges are either positive (+) or negative ()
- Charge results from the presence of electrons (e) or protons (p+), and a charged region in space results from a net excess of electrons or protons.
- Charge is represented by q.
- Charge is measured in coulombs; one coulomb of charge equals the amount of electrical charge in 6.241506 ×1018 electrons, protons, or other charges.
Electric potential
• Electric potential is the form of energy that makes charges tend to move.
o It thus serves as the driving force for movement of charges.
o Electric potential can also be thought of as the tendency for charges to move.
o We usually drop the “electric”, and just refer to potential.
How is potential measured?
• Potential is measured in units of volts (V) or millivolts (mV).
o Potential is variously represented by V, E, , or .
o We will usually use V or , but your physics buddies probably prefer E.
What causes charges to move?
• A region of net negative (or positive) charge is surrounded by a potential field, and the energy in this potential field will cause charges to move.
o The more charges in a region, the stronger the potential field surrounding the charged region
o The ‘strength’ of the potential field – and therefore the tendency of charges to move – decreases exponentially with distance:
The more charges in a region
o the stronger the driving force for current flow, and
o the farther the field extends outward from the edge of the region containing the charges.
the potential difference between two regions depend on:
- the amount of net positive or negative charge in each of the regions.
a. more net charge = more separated charge = greater potential difference greater tendency for charges to flow between the two regions. - the distance separating the charged regions.
a. For a given amount of separated charge, increasing the distance between the charged regions decreases the strength of the potential field between them decreased tendency for charges to flow between the two regions.
What can we say about potential differences in biological systems?
o No separated charge = no potential difference no tendency for charges to move.
o The greater the amount of separated charge, the greater the potential difference (i.e., the driving force), and therefore the greater the tendency for charges to move.
Current
- Current is simply the movement, flow, or flux of charge
- In solids, the flowing charge is usually electrons; in liquids, it can be either electrons or ions. In biological systems, current almost always involves ions. In this course we’ll make frequent reference to sodium, potassium, calcium, and even chloride currents.
- Current is usually represented as I, occasionally as A.
- The unit is the ampere; 1 ampere = 1 coulomb of charge moving past a point in one second.
Resistance
• The resistance of a medium (a copper wire, a plasma membrane, cytoplasm, etc.) measures how difficult it is for charges to move through the medium. This is true whether the charges are in the form of electrons or ions.
Resistance is represented by R, conductance by g.
Resistance and conductance are inversely related:
g=1⁄R⟺R=1⁄g
The unit of resistance is the ohms, represented by the Greek letter omega (Ω).
Conductance
- Conductance measures how easy it is for the charges to move through the medium.
- Unit of conductance is Siemen
capacitance
ability to store (separated) charge. Measured in farad. (1 C/volt) (amount of charge per unit of driving force)
Ohm’s law
- V=IR
- potential= current X resistance
- in other words: current=conductance X potential
- “the current is equal to the driving force tending to cause current to flow multiplied by the ease with which charges can flow”
Potential differences in biological systems
systems result from separation of positive and negative charges, and the greater the amount of separated charge, the greater the potential difference.
current in biological systems
is usually the result of moving ions such as Na+, K+, Ca++, or Cl, rather than moving electrons
potential differences are
the driving force for current, and the larger the potential difference, the larger the current, all else being equal
Ohm’s law can be rearranged to yield form that
described the dependence of current on conductance and potential: I=gV
Capacitor experiments show:
o resistance reduces the rate at which current moves in response to a potential difference.
o potential differences cause current to flow, and
o current flow can create or destroy the charge separation that produces a potential difference.
ionic basis for action potentials
have ion channels that are proteins that span the PM like a tube. This allows for aqueous passageway of ions
non gated ion channels
open all the time, facilitated diffusion based on concentration
gated ion channels
Have different conformations (open and closed)
Specific ion activity for an action potential
- at threshold, increase in conductance in the membrane for Na+
- at tip of spike- reversal of Na+ conductance
- at spike and after spike, large increase in the conductance in the membrane for K+
- at rest: conductance for Na+ is 1, conductance for K+ is 30.
- at threshold conductance for Na+ is 700
- at spike: conductance of Na+ is 1 and for K+ it’s 250
What happens after potential?
membrane becomes hyper polarized and there is a gradual reversal in the K+ conductance
What determines the magnitude of potential?
Amount of separation in charge. the K+ efflux determines the potential and the sign
What determines the threshold?
Na+ influx
How are the driving forces of Na+ and K+ related?
They are the same
voltage-gated Na+ channel
conformation depends on membrane potential
When is the Na+ channel open?
Any time the membrane is less negative than the threshold. The activation gate is open and Na+ can diffuse.
When is the Na+ channel closed?
At rest, the filters are super close together and Na+ can’t diffuse. This is the activation (M) gate. It is normally closed, but is open for whole spike in an action potential
H gate
inactivation gate. Closes Na+ gate after it is open. Activation of M gate triggers activation of H gate. At the left side of the spike?
propagation of action potentials
action potentials change inside/outside charges. each one triggers the next region of charges to change.
non decremental propagation
does not lose intensity as it moves down an axon
-caines
xylo-, pro-, lido-, benzo-, novo-, co-
bind to voltage gated Na+ channels and prevent opening activation gate; stop action potentials signaling pain
opiates
block affective response to pain; just don’t care that it hurts
how is an action potential propagated?
- influx of Na+ at start of action potential repels intracellular cations causing them to spread away from sodium channels
- as positive charges are pushed further from initial sodium channels, they depolarize adjacent portions of the membrane
- nearby voltage-gated Na+ channels open when the membrane reaches threshold, resulting in an action potential
Why are action potentials all or none/
Action potentials are continually regenerated at adjacent areas of PM (on an axon)
Why don’t action potentials move backward on an axon?
- Refractory period: once Na+ channels have opened and closed they are less likely to open again for a short period. therefore “upstream” gates are in refractory states
- also helped by hyperpolarization phase after an action potential.
local circuit theory
how action potentials move along an axon; positive charges move in response to moving negative charges
local circuit theory of propagation (from online)
A generally accepted model for neuronal conduction, by which depolarization of a small region of a neuronal plasma membrane produces trans-membrane currents in the neighboring regions, tending to depolarize them. As the sodium channels are voltage gated, the depolarization causes further channels to open, thus propagating the action potential.
synaptic transmission of action potentials
can be electrical or chemical
electrical synapse
direct physical contact between cells for information to pass
chemical synapses
transmission of action potential between cells involves a chemical mediator that is released by one cell and picked up by another
synapse
synaptic bulb and PM of post synaptic nuron
synaptic vesicles
holds neurotransmitters; 10^4 of ACh in each vessicle
SNARE complex
protein that allows vesicles to fuse with the PM and release the neurotransmitter.
Acetylcholinesterase (ACHase)
degrading enzyme for ACh; high activity enzyme
reuptake transporter
takes in choline after it is degraded
sub synaptic membrane
part of the post synaptic neuron that is associated with the synaptic bulb; has ACh receptor; has Na+/K+ channel that is normally closed
action potentials on the synaptic bulb
spread all over it
Ca++ channels in synaptic bulb
- in cytoplasm of the synaptic bulb; one of the only places you find them
- voltage-gated
- Ca++ is intracellular second messenger
- required to activate SNARE complex (Na+ can’t do this)
How is SNARE activated?
- by Ca++
- similar way as muscle fibers
- move vesicles open to extracellular space and dump out ACh
exocytosis
release of neurotransmitter
-this creates gradient to allow for diffusion of ACh across the synaptic gap
What happens when ACh binds?
chemically gated ion channels open
- Na+/K+ channels
- the conductance increases until the conductance is equal
- this decreases the membrane potential
EPSP
excitatory postsynaptic potential
- 1-2 volt peak after ACh binds
- really short and really weak
IPSP
inhibitory post synaptic potential
-the membrane potential after ACh binds
depolarization to threshold
change in membrane potential of 10-40 mV
choline
(after being separated by AChase) gets transported back into synaptic bulb by reuptake transporter protein to be reused
summation
spatial and temporal
summation text book
look this up
What happens when a K+ channel is opened?
sometimes when the neurotransmitter binds a K+ channel opens up and increases the K+ efflux. This increases the membrane potential (hyperpolarized) and is associated with the IPSP
Sensory physiology
- Stimulus energy
- absorbed by appropriate receptor
- change in membrane conductance for one or more ions
- change rates of flux of ions through membrane (J)
- change in membrane potential (depolarization or hyperpolarization)
- change in action potential frequency
- signals to the brain
What does a change in action potential convey?
- Conveys information about presence/absence of a stimulus
2. stimulus strength; frequency is proportional to the log of the stimulus intensities (not linear)
electrical activity of the heart
pacemaker potential
cardiac muscle fibers
- striated
- branched
- interconnected by electrical synapses
- myogenic
- functional syncitium
myogenic
don’t require connection to the nervous system to beat; generates its own action potential
functional syncitium
behave as a single cell
Action potential in the heart
action potentials spread through atria and contractions influence ventricles to contract too
Action potentials in the SA node
can’t spread action potentials directly from atria to ventricles because of barrier; have to go through AV node
AV node and bundle of His
- AV node is connected to bundle of His
- Bundle of His
- two clusters of conduction cardiac cells (bundle branches)
- -take action potentials to apex of ventricles
- -action potentials spread throughout ventricles; pumping blood out of arteries
SA node rates
in a typical person the SA nodes generates action potentials at 60-80 per min
AV node rates
AV node generates action potentials at 40-60 a mins and can take over if SA node fails
Bundle of His rates
generates action potentials at 30-40 per min
SA node cells
have high conductance of Na+ and Ca++; so high that a resting potential is never acheived
Ach and heart rate
-causes a significant increase in conductance of K+; hyperpolarizes, slows down heart rate
Norepinepherine and heart rate
- increases conductance of Na+ and Ca++
- depolarizes
- increases rate of decrease of K+ conductance during prepotential
- doesn’t reach the same hyperpolarized potential (steeper slope to get to threshold)
- increases heart rate
Cardiac Cycle
- Ventricles contract; ejection of blood; systolic phase
2. Ventricles relax; cardiac filling; diastolic phase
Regulation of cardio vascular system
- cardiac output
- volume of blood ejected by heart per beat and per min - Distribution of blood/output
How do we define potential in the electrical sense?
The form of energy that makes charges tend to move, this is a driving force; “the tendency for charges to move”
How do we define current in the electrical sense?
The movement, flow, or flux of charge; usually ions in biological beings
What is responsible for current in a copper wire? What is responsible for current in most biological systems?
In copper wire, the current is made by moving electrons, in biological systems it is made by moving ions
What do we mean by the term membrane potential?
the separation of charge on either side of the membrane (inside the membrane versus outside of the membrane) The tendency for things to move
Potentials – of batteries, electrical outlets, or membranes – are measured in units of ____________________?
Volts or milivolts
In biological systems, potentials results from _____________________________.
Separation of charges
What is meant by the term conductance?
a measure of how easy it is for charges to move through a medium; the inverse of resistance
Role of K+, Na+, non-diffusible anions (A-).
These are responsible for creating the membrane potential. There concentration inside and outside of the membrane determines the magnitude and the sign of the difference in charge
The importance of membrane conductance for K+, Na+, and A-.
A- are stuck in the membrane and contribute the negative charge that is normally present on the inside of the cell, K+ and Na+ are conducted through membrane proteins. A- diffuse into the cell by hitching a ride with K+
The importance of rates of Na+ and K+ flux through the membrane.
For every one Na+ ion that passes through the membrane, 30 K+ leave the cell. This is important in order to maintain the negative charge in the cell during a resting state.
Under most circumstances, the primary determinant of the magnitude of the resting membrane potential is _________________________________________. Why is this?
The efflux of K+ ions, because this is happening at a rate 30 times greater than the influx of Na+ ions. This highly offsets the change in charge from the influx of Na+ ions
The effect of Na+ on resting membrane potential is to ______________________.
Cause depolarization to allow a membrane to reach threshold and result in an action potential
discuss the ionic basis for an action potential.
At rest, the conductance for K+ is 30 and the conductance for Na+ is 1 (polarized). When the membrane reaches threshold, ion gated channels allow for the increased conductance of Na+ ions (depolarization), at the spike of the action potential, the conductance for Na+ reverses, and the conductance for K+ increases, this results in hyperpolarization and the membrane slowly reverses the conductance for K+.
According to your textbook, how do action potentials progress from place-to-place along an axon
Positive charges push further away from initial sodium channels depolarize adjacent portions of the membrane; this causes more action potentials in the adjacent areas of the membrane; they also exhibit a refractory period where the sodium channels are less likely to open again; also the hyperpolarization that occurs after each action potentials makes it more difficult to reach threshold
What is meant by the term refractory period, and why is it important in neuron function?
Once sodium channels have opened and closed they are less likely to open again for a short period; this allows for action potentials to move forward along the neuron because “upstream” gates are in a refractory period
What is the mechanism of action of tetrodotoxin (TTX) and novocaine? What effects do they cause?
These bind to the voltage-gated Na+ channels and prevent opening of the activation gate; can stop action potentials signaling pain.
How do inhibitory synapses differ from excitatory synapses? Are inhibitory synapses important in functioning of your nervous system? Justify your answer with some evidence.
In excitatory synapses, an action potential in the presynaptic neuron increases the probability of an action potential occurring in the post synaptic neuron. In inhibitory it is the opposite. They are both important for either starting and continuing a signal or in shutting down a signal.
Regulation of CV function
intrinsic or extrinsic
intrinsic
no input from NS or hormones: local blood flow, autoregulation of cardiac output
Blood flow path
left ventricle, aorta, large arteries, small arteries, arterioles, metarterioles, capillaries, venules, small veins, large veins, right side of heart, left side of heart
large arteries
carotid, renal, hepatic, femeral, pulmanary
microcirculation
arterioles, metarterioles, capillaries, venules
capillaries
main site of exchange between blood and tissues
Properties of all veins and arteries (not capillaries)
have thick smooth muscle coats/layers in their walls
why don’t capillaries have smooth muscle?
Because it would get in the way of the exchange
Smooth muscle in arteries
- spontaneously generate action potentials and spontaneously contract
- contraction= vasoconstriction (increased resistance to blood flow) causes shunting of blood elsewhere (mostly arterioles, metarterioles, and small arteries) - Forced to relax by “something”
- vasodilation (decreased resistance to blood flow)
Smooth muscle cells in veins
Contraction causes change in compliance (ability to hold/move blood) and change in volume (can lead to pooling)
Veins have thinner, flexible walls
compliance (veins)
ease of stretching; veins exhibit significant changes in diameter
Capillary exchange between metarteriole and venule
- precapillary sphincter open
- blood flow through capillaries
- exchange of O2, CO2, H+, nutrients, waste, etc
- precapillary sphincter closes
- no blood flow through capillaries
- depletion of good stuff, and accumulation of bad stuff
- precapillary sphincter forced to relax
repeat
increased metabolic demand of tissue
sphincters would be open more; increased blood supply
Prolonged increase in metabolic demand (few days or weeks)
release angiogenin; increase in microcirculation components; increased tissue vascularization
-this is reversible if you stop having the demand for it
increased stretching in cardiac muscle fibers
automatically contract
autoregulation of cardiac output
venus return; ventricular filling; ventricular myocardium degree of stretch; strength of contraction during systolic phase; determines ejection volume; end-diastollic volume
End diastolic volume (EDV)
amount of blood left in heart after contraction and blood flowing back in
two factors influence degree of stretch (systole)
EDV and venous return
Extrinsic
explicitly involves organs and tissues external to VS; like blood pressure
What are pacemaker potentials and what are they useful for?
They are the electrical activity of heart, action potentials made from the SA node
Present a detailed version of the ionic basis of the pacemaker potentials generated by the SA node.
To reach threshold, there’s an increase in conductance of Ca++ and Na+, then when it reaches the peak the conductance for Ca++ and Na+ decreases and the conductance of K+ increases. After the potential is over, the conductance for K+ slowly decreases
How do acetylcholine (ACh) and norepinephrine (NE) impact pacemaker activity of SA node cells. In terms of cardiac output, what are their effects?
ACh slows down the activity of the SA node and causes a decrease in cardiac output (it does this by slowing down the decrease in K+ conductance after an action potential). NE causes an increase in the activity of the SA node and an increase in cardiac output. It does this by increasing the rate of decrease in K+ conductance after an action potential.
What is stroke volume?
The amount of blood pumped out of the heart (left ventricle to the body) during each contraction, measured in mL
Cardiac output equals the product of what two variables?
Heart rate and stroke volume
Intracellular Ca++ is required for contraction by all muscle fiber types. What is the major source of Ca++ for cardiac muscle fiber?
Sarcoplasmic reticulum
** outside of the cell
Present a detailed description of the Intrinsic Regulatory Mechanisms that I discussed in lecture
Local blood flow from left ventricle, aorta, large arteries, small arteries, arterioles, metarterioles, capillaries, venules, small veins, large veins, right side of heart. They are part of a negative feedback loop because they are based on the metabolic needs of the tissues.
What is tissue vascularization and how is it relevant/important to discussion of regulation of the cardiovascular system?
The amount of blood vessels available in the tissue. Metabolic demand releases angiogenin that increases mitochondrial components and vascularization. So the higher the need for the cardiovascular system, the higher the vascularization.
Describe propagation of action potentials from the SA node through the rest of the heart.
SA node, to AV node, to bundle of His, to apex of the ventricles
Discuss voltage-gated sodium channels and their role in action potentials. Why do we say that they’re “voltage-gated”?
They are voltage gated because their conformation (open and closed) depends on membrane potential, open any time the membrane is less negative than threshold.
Summation
if several EPSPs occur together close in space and time they can sum and make the membrane more likely to reach threshold and fire an action potential. A single EPSP causes a short-lived change in membrane potential
What do we mean when we say that receptors are selective transducers?
Because they are specific to certain ion levels
The types of blood vessels
- Arteries: are tough, thick walled vessels that take blood away from the heart; small arteries are called arterioles
- capillaries: vessels with walls one cell thick allowing exchanges of gases and other molecules between blood and tissues; networks of capillaries are called capillary beds
- veins: thin walled vessels that return blood to the heart; small veins are called venules.
Sphincter (as it applies to blood vessels)
ring of smooth muscle makes the precapillary sphincter; when the metabolic demand of the tissues increases, sphincters would be open more and this would increase blood supply
capillaries
smallest blood vessels, suitable for exchanges in gases, nutrients, and wastes between blood and other tissues
A key aspect of regulation of the cardiovascular system is a hierarchy of control. How is this illustrated in my lectures on regulation of the cardiovascular system? Can you think of any reason(s) that hierarchical levels of control should be so frequently encountered in various physiological systems?
-SA node generates action potentials at 60-80 per min
-AV at 40-60
-Bundle of His at 30-40
These other mechanisms can take over if the SA node fails to generate the action potential. This is important because physiological systems are very dependent on the cardiovascular system having continuous function. Having a hierarchy allows for things to take over if something higher up fails to allow for continuous function.
