bmsc 207 neuro Flashcards
membrane potential
the electrical disequilibrium that exists between the ECF and ICF (more negative) is called the membrane potential
in the beginning the cell has no membrane potential
equilibrium potential
for any conc gradient of a single ion , the membrane potential that exactly opposes the conc gradient
E ion for example E k or E na
the amount coming out will be the same as the amount being drawn in making it a equilibrium potential no more net movement when reached -90mV for potassium
equilbrium will be reached
sodium is outside the cell and is positively charged and a leak channel would open, causing the sodium to come into the cell and repel some sodium, eventually where the amount coming in and repel is the same which +60mV
Nernst equation
used to find the equilibrium potential for an ion
need to know conc gradient of the ion and the charge of the ion
resting membrane potential
membrane potential of a cell when it is not active
-70mV
the sodium potassium ATPase maintains it but mainly K+
why K+ creates the resting membrane potential
due to the memrbane being more permeable to K+, K+ flows out faster than Na flows in
40 times more permeable to K
EK=-90mV
ENa= +60mV
disturbance of resting membrane potential (two factors)
two factors
1) the conc gradients of different ions across the membrane (Na, K, Cl and Ca) changes in the conc gradient results in alteration of membrane potential
2) the permeability of the membrane to those ions, open gated channels, sodium gated channel opens makes higher sodium making membrane channel depolarize, if you open additional potassium gated channels have even more potassium leaving making the membrane potential hyper-polarize more negative, open Cl gated channel cell would hyperpolarize
what maintains the resting membrane potential?
Na-K ATPase
sets up the conc gradients that determine membrane potential
3 Na out and 2 K in
maintains the conc gradients for Na and K
how the resting membrane potential is set up (sodium/potassium)
-sodium and potassium channels will be inserted
-the amount of potassium
leaving is higher than the amount of sodium coming in because there are more k leak channels
making the cell negative
-as the cell become negative potassium goes down its conc gradient, some of it gets drawn back in but there is more leaving, making the cell more negative
for sodium we have more sodium being drawn in by the negative charge
conc gradient and the electrical charge draws the Na in
as cell more - the movement of K out slows down and the amount of sodium coming in fast for how little of leak channels because of electrical charge and the conc gradient
reaches equlibrium the net movement of potassium outward= the Na coming in at -70
nervous system
coordinates voluntary and involuntary actions and transmits signals to and from different parts of its body
rapid
2 main branches
CNS brain and spinal cord acts as the main integrating part of the body
peripheral nervous system any nervous tissue outside the brain and spinal cord
afferent vs efferent
efferent takes information from the CNS to target cells via efferent neurons (somatic motor and autonomic subdivison sympathetic/parasympathetic motor)
afferent bring info toward the CNS
subdivisons: somatic, visceral, special sensory
which of the following statements about the resting membrane potential is true?
it results in part from the permeability of the cell membrane to K+
neurons/glia
neurons: the basic signalling units of the nervous system
glia: support cells
soma, dendrites, axons, presynaptic terminals
soma: a cell body, considered the control center, with processes that extend outward, dendrites and axons
dendrites and axons number/length vary from neuron to neuron
dendrites: receive incoming signals from neighbouring cells
axons: carry outgoing signals from the inegrating center to target cells
presynaptic termianls: contain transmitting elements
afferent/efferent (sensory/motor)
afferent: sensory
- carry info about temperature, pressure, light and other stimuli to the CNS
Efferent: motor and autonomic
motor: control skeletal muscles
autonomic: influences many internal organs
sympathetic and parasympathetic
usually have axon terminals or varicosities
interneurons
complex branching neurons that facilitate communication between neurons
axonal transport
axon convey chemical and electrical signals that require a variety of different types of proteins
the axon contains many types of filaments and fibers but lacks ribosomes and ER necessary for protein production,
*proteins must be produced in the cell body (soma) then transported down the axon
different types of neurons
and structural categories
sensory neurons: senses like temperature, vision, hearing
pseudounipolar: only one axon of the soma but then splits into 2 separate axons
Bipolar: one single axon on each end has 2 poles, sensory neurons aswell
vision and smell, have transduction channels
interneurons of CNS: found only in the CNS so within the brain/spinal cord,
anaxonic: dont have an axons have bunch of dendrites
multipolar: has multiple axons and dendrites off the soma
typical multipolar efferent somatic motor neurons look like this, be very long,
axonal transport (speeds and direction)
fast: smaller proteins membrane bound proteins and organelles (vesicles or mitchondria)
anterograde: axonal transport from soma to the axon terminal, up to 400 mm/day
retrograde: axonal transport from axon back to the soma , 200 mm/day
slow: larger proteins, cytoplasmic proteins (enzymes) and cytoskeleton proteins
mainly anterograde, up to 8 mm/day, some evidence for retro
kinesins and dyneins: motor proteins
kinesins: anterograde transport
dyneins: retrograde transport axon t towards the soma
synapses (pre, cleft, post) types
point of communication between a neuron and another cell
2 types: chemical (majority) uses chemical to communicate with the other cell
electrical
presynaptic cell: release chemical signal that goes to receptors on the post synaptic cell that causes a cellular response , synaptic cleft between
How do billions of neurons in the brain find correct targets during development?
depends on the chemical signals
growth cones that sense and move towards particular chemical signals
myelin forming glia
myelin is a wraping around a axon from another cell
oligodendrocytes- CNS many segments of myelin in one cell
Schwann cells-PNS around the whole cell, each segment is 1 schwann cell
provide structural stability, insulation around the axon to speed up electrical signals, supply chemicals that are needed
demyelination
multiple sclerosis: disorder resulting from demyelination in brain and spinal cord
MS symptoms: sensory, motor and cognitive issues
immune cells attack myelin
scar tissue and myelin and wont be able to reform
satellite glial cells
surround the soma
exist within ganglia (bundles of cell bodies) in the PNS
form a supportive capsule around the cells bodies of neurons (sensory and autonomic)
supply nutrients
structural support
astrocytes (where are they found and function)
shaped like a star
highly branched glial cells in the CNS
half the cells in the brain
functions: take up and release chemicals at synapses
provide neurons with substrates for ATP production
helps maintain homeostasis in the ECF
surround vessels (part of the blood brain barrier and influence vascular dynamics)
microglia
specialized immune cells that reside in the CNS
serve to protect and preserve neuronal cells from pathogens and facilitate recovery from metabolic insults
if the signals that activate microglia pass a threshold or the microglia remain activated past a certain time period, there can be deritmental properties, alzheimers, ALS
ependymal cells
line fluid filled cavities in the brain and spinal cord
help to circulate cerebrospinal fluid that fills these cavities and surrounds the brain and spinal cord
- protection
- chemical stability
-clearing wastes
peripheral neuron injury
can CNS repair?
CNS repair is less likely to occur naturally, glia tend to seal off and form scar tissue
in the peripheral, there are Schwann cells that help regenerate
schwann cells can get rid of other schwann cells that are not attached to the neuron
schwann cells in regeneration
can create a tube to guide the regenerating axon
1mm/day in small neuron
5mm/day in a large neruon
it can take a long time months
like a nerve runnnig from toe to quad can take months
why neurons are excitable?
neurons and muscle cells are excitable due to their ability
to propagate electrical signals over long distances in
response to a stimulus
the change in membrane potential and that change can be transferred to a muscle fiber or axon
response to stimulus
Goldman-Hodgkin-Katz equation
predicts membrane potential that results from the contribution of all ions that
can cross the membrane
determined as the combined contribution of each ion (concx permeability) the mem potential
*different from Nernst, which calculates the equilibrium for a single ion
5 major types of ion channels
1) Na
2) K
3) Cl
4) Ca
5) monovalent cation channels (allow Na and K to pass)
gated channels (3 types)
ion permeability is primarily altered by opening and closing of gated channels
mechanically gated channels: open in response to physical forces found in sensory neurons, allow sodium/calcium to come in
chemically gated ion channels: in neurons responding to ligands, including extracellular neurotransmitters and neuromodulators or intracellular molecule
ex)nicotinic receptor, more chloride coming in
voltage gated channels: respond to changes in the cell membrane potential
low threshold voltage gated meaning small change mem potential can open the gate
and some need big change in depolarization (high threshold)
ion movements create electrical signals
Concentration gradient usually does not change when there are changes in membrane potential,
a change in the K concentration gradient or change in permeability to ions (Na,K,Ca, or Cl) alters the membrane potential
a huge change in the membrane potential (-70mV to +30mV) does not indicate a change in conc gradients of a given ion
only a tiny amount of ions are needed to change membrane potential
conductance of a ion
the ease with which ions flow through a channel
current flow and Ohms law
the opening of ion channels allows ions to move in and out of the cell
current flow is directly proportional to the electrical potential difference (in volts) change in mem potential between 2 points and inversely proportional to the resistance
resistance as ions move through fluid into the cell there is friction
two sources of resistance in a cell
membrane resistance: resistance of phospholipid bilayer
internal resistance of the cytoplasm: cytoplasmic composition and size of the cell
resistance will be determined how far the current will flow in a cell before the energy dissipate
what is ion current
the flow of electrical charge carried by an ion
current follow ohms law
electrical signals in neurons
graded potential: generated in the dendrites and soma, variable strength signals (meaning very big or small) travel over short distances and lose strength as they travel. can be depolarizing or hyperopolarizing. if graded potentials create a large enough depolarization, it can induce an action potential
Action potentials: generated axon hillock, very brief, large depolarizations that travel long distances through a neuron without losing strength. rapid signals over long distances
how and where is graded potential generated
generated in the soma and dendrites
generated by chemically gated ion channels or closure of leak channels (CNS and efferent neurons)
size is proportional to the size of the stimulus
excitatory vs inhibitory (EPSP or IPSP)
depolarization is excitatory postsynaptic cell, and hyperrpolrization is inhibitory post-synaptic potential
trigger zone (axon hillock + AIS)
the region determines if an AP will be generated
find high conc of voltage gated sodium channels
threshold is -55mV or more positive will activate the sodium channels causing an AP
subthreshold vs suprathreshold graded potential
subthreshold (NO AP): graded potential starts above threshold but decreases in strength as it travels through the cell body. at the trigger zone it is below threshold meaning no AP
suprathreshold (AP): stronger stimulus at the same point on the cell body that creates a graded potential that is higher than threshold by the time it reaches trigger zone, so initiates an AP
Action potential (the sodium)
the sodium that comes in will travel to the next area keep going and going like a domino effect.
ap generated here then the next then the next adjacent region
conduction of AP
movement of AP along axon
conduction of AP requires few types of ion channels: voltage gated Na and K channels as well as the leak channels that help set the resting membrane potentiall
Action potential steps
RMB -70mV depolarizes to threshold (-55mV) AP activated
Rising phase (depolarization)
depolarizing stimuli voltage gated sodium channels (-55mV), allow Na to travel down electrochemical gradient at +30mV channels inactivate
falling phase (repolarization)
voltage gated K channels also open in response to the depolarization, but do so more slow than Na channels
after hyperpolarization phase: voltage gated K do not immediately close when reaching -70mV causing membrane potential to dip below the resting membrane potrential
leak channels bring membrane potential back to -70mV
Na-K ATPase brings ions back to orginal compartmets (this doesnt have to happen befoe another AP is triggered)
comparison b/w AP and Graded potential
type of signal: graded input signal action regenerating conduction signal
gated channels involved: GP mechanically, chemically, or voltage, AP just voltage
ions involed: GP Na K Ca AP just K and Na
unique characteristics: graded no min level to initiate well AP threshold is required to initiate,
AP signals cant sum because of refractory period
how do voltage gated Na channels suddenly close at the peak of AP
contain two gates: activation gate and inactivation gate
activation in the central region of the pore
inactivation is a sequence of amino acids on the cytoplasmic side
inactivation is slower both have threshold of -55mV
at the resting membrane potential, the activation gate closes the channel
depolarizing stimulus arrives at the current. activation gate opens (-55mV)
with activation gate open, Na enters the cell quickly
inactivation gate closes and Na entry stops
ones open and one closes activation faster and inactivation slower
during repolarization the two gates goes to orginal state
absolute refractory period and relative refractory
absolute: a second AP can not be initiated 1-3msec
relative: a second AP can be generated but requires a larger than normal graded potential 2-5msec
larger because you are at a more negative state
refractory period (purpose)
ensures AP travels in one direction
limits the rate at which signals can be transmitted down the neuron -prevent excitotoxcity information is often encoded in the frequency of AP
action potential are conducted (propgated)
1) graded potential enters the trigger zone
2) voltage-gated Na channels open, Na enters the axon
3) positive charge (Na) spreads along adjacent sections of axon by local current flow
4) local current flow causes new section of the membrane to depolarize
5) loss of K repolarizes the membrane
6) the refractory period prevents backward conduction
*ap cant move backward because the previous region that was depolarized and will be in the absolute refratory and the time it gets out the ap will be way down the axon
velocity of conduction (axon)
two physical parameters determine the velocity:
1) the diameter of the axon: a large diameter axon will offer less internal resistance to current flow more ion will flow in a given time
in large diameter there is less resistance more ions can come in, in a small one it is less rapid of ions coming in
2) the resistance of the axon membrane to ion leakage: current will spread to adjacent sections more rapidly if it is not lost via leak channels
conduction velocity is more rapid in myelinated axon (blocking/ nodes of ranvier)
AP conduction is more rapid in axons with high-resistance membranes (decreased current leak)
Nodes of ranvier contain abundance of Na channels, that exist between myelinated regions
myelin is wrapping the region so all the leak channels are blocked so no current loss
most of the Na will flow to the next section
myelinated axons have larger axon diameter
saltatory conduction
get to skip channels
conduction occurs from node to node
it is faster than a unmyelinated axon conduction velocity
nodes of ranvier
demyelination (MS)
failure of conduction
lose the myelin
only nodes contain Na channels, The AP cannnot be maintained in the unmyelinated region due to a lack of Na channels
alot of sodium is lost due to the leak channels and the next region wont reach threshold causing AP to stop
chemical factors can interfere with conduction
by binding to Na, K, or Ca channels in the neuron
ex) local anesthetics
the dentist
the chemical binds to voltage gated sodium channels, it stops action potentials in mouth, when you go to the
graded potentials still being produced but then it stops because the voltage gated channels are blocked
normokalemia, hyperkalemia, hypokalemia
normokalemia: normal plasma
potassium in a normal range
subthreshold graded potential does not fire AP
normokalemia above threshold will fire a AP
hyperkalemia: (depolarizes the cell) trigger AP a excess of potassium in the extracellular fluid
this causes neuron to fire when not suppose to because the resting membrane potential depolarized because conc gradient has changed
intra stays the same but extra goes up
less potassium leaking out making cell more positive (depolarizing)
hypokalemia : hyperpolarizes the cell, make the neuron less likely to fire an AP in reposne to a stimulus that would normally be above threshold
not trigger AP
electrical synapses vs chemical synapses
electrical: some cns neurons, cardiac muscle, smooth muscle, very fast faster than chemical
ap is propgated down and Na goes through gap junctions
chemical: majority of neurons in the nervous system use chemical signals to communicate from one cell to the next
electrical signals from presynaptic cell is converted to a neurocrine signal that crosses synaptic cleft and binds to receptor to post synaptic cell
neurocrine
a chemical substance released from neurons used for cell to cell comunication:
1) neurotransmitters
2) neuromodulators
3) Neurohormones
neurotransmitters, neuromodulators, neurohormones
neurotrasnmitters: chemical is released in one neuron, acts on a post synaptic cell in close vincity and causes rapid response in the postsynaptic cell
neuromodulators: chemical released by one neuron, bind to receptor in posysynaptic cell in close vincity but its a slow response in the poostsynaptic cell
the same neurocrine can act as a neurotransmitter at one synapse and neuromodulator at another depending on the receptor present
neurohormones: are secreted into the blood stream and act on targets far away not localthroughout the body
paracrine or autocrine
Autocrine, when the chemical releases acts back on the neuron that releases it
paracrine: signal in the local vincity, usually the cell has to be close for the pre synaptic to affect the post synaptic
neurocrine receptors
1) ionotropic receptor (ligand gated ion channels)
-neurotransmitters create rapid potential
ligand binding to iontropic receptors causes a opening of a channel
can be specific for one ion (Na, Ca, K, Cl) or a non selective cation channel
mediate fast postsynaptic responses
2)metabotropic receptors (G-protein coupled receptors)
neuromodulators create slow synaptic potential and long term effects
slower responses
cytoplasmic tail of recepotor is linked to three part membrane transducer protein (g-Protein)
ligand binding to metabotropic receptor leads to a g protein mediated cellular esponse
i) interact directly with ion channels -can lead to opening or closing of a channel depending on g-protein
ii) activate membrane bound enzymes
two main types: A) phospholipase C signal transduction pathway
B) adenylyl cyclase signal transduction pathway
neurotransmitters are released from vesicles (synethsis)
vesicles containing neurotransmitters accumulate in the axon terminal ready to be released on demand
synthesis
large peptide neurotransmitters ae produced and packaged into vesicles at the soma and transported (fast axonal transport)
small neurotransmitters are synthesized and packaged at the axon terminal (majority)
neurotransmitters release
occurs via Ca mediated exocytosis
a bunch of voltaged gated Ca channels
1) an AP depolarizes the axon terminal
2) the depolarization opens voltage gated Ca channels and Ca enters the cell
3) calcium entry triggers exocytosis of synaptic vesicle contents
4) neurotransmitter diffuse across the synaptic cleft and binds with receptors in the post synaptic cell
5) neurotransmitters biding initiates a response in the post synaptic cell
