L7: Electrical signalling

hodgkins and huxley

• pioneers of electrical signal and neurophysiologly

• worked with squid axon

• gained electrical signals from axon

• first to show live intracellular recording of an AP

squid axon length

• 1mm diameter

• 1 meter long

functions of nerves

• carry signals from sensory organs to the CNS

• carry signals from CNS to muscles and other organs

• transmist and process signals within CNS

nerve conduction

movement of electrical signals

neuron function

transmit nerve impulses

how many neurons in humans

86 billion

dendrite functions

• receive electrical signals

• receive info simultaneously from various presynaptic cells

how does signal travel from one neuron to another

• dendrites receive electrical signals

• signal travels down cell body

• if signal is strong enough, it generates an AP when it reaches the axon

• axon covered in myelin sheath which speeds up AP

• signal makes it to synapse to the postsynaptic target

unipolar neuron

• one axon

• fused dendrites

• long sensory neurons

• some of the longest neurons

bipolar neuron

• distinct dendrite/axon

• small

• rare

• in the CNS (interneuron)

multipolar neuron

• most common

• more than one dendrite branch

• one axon

• long motor neurons

pseudounipolar neuron

• one axon, and one axon/dendrite

• sensory neurons

• dendrite exhibits axon properties

• not clear where dendrite and axon begins

neurogenesis

• birth of new neurons

• continues into adulthood

• new neurons develop everytime you learn smth new

what promotes neurogenesis

• avoiding stress

• stress degrades neurogenesis

draw every neuron 

x

glial cells

• support, help and take care of neurons in place

• 10 glial cells per neuron

• diff glial cells in CNS vs PNS

glial cells in the CNS

• ependymal cells

• microglia

• astrocytes

• oligodendrocytes

ependymal cells

• assist in producing, circulating, monitoring cerebrospinal fluid

• CSF fills the brain-skull gap

• protects brain and neurons

• makes sure that the fluid is present in optimal levels for neurons to function properly

microglia

• mobile phagocytic cells that remove cellular debris, waste products and pathogens

• pacman

• collects garbage between neurons

astrocytes

• maintains the blood/brain barrier

• structural support

• regulate ion, nutrient and gas concentrations in interstitial fluid around neurons

• absorb/recycle NTs

• form scar tissue after injury

blood-brain barrier

seperation of blood in capillaries from neurons

oligodendrocytes

• provides CNS framework by stabilizing axons

• produce myelin

• wraps axon with layers of myelin and plasma membrane, creating myelin sheath

myelin

• insulator

• made up of proteins and fats

• helpful for long neurons

• preserves charges

• speeds up nerve conduction

• AP does not have be produced repeatedly

2 types of glial cells in the PNS

• schwann cells

• satellite cells

schwann cells

• neurolemmocytes

• cover peripheral axons

• participate in axon repair

• made out of myelin so wraps itself around cells repeatedly

satellite cells

• surround peripheral cell bodies

• regulate environment around neurons

• similar to astrocyte role

cells at rest equilibrium

• high KCl concentration inside cell

• high NaCl concentration outside cell

what happens if the cell membrane has no receptors

• impermeable to ions

• ions are stuck where they are

cell membrane when K exits the cell

• K leaves cell through open channel passively

• cell membrane is semipermeable to K

• still impermeable to Na

• selectively permeable

what happens when K leaves the cell

• wants to form equilibrium

• before the eqm mark, is repelled by Na’s positive charge

• as a result, some K remains inside the cell

coulomb force

• attempt to balance K and Na concentration inside and outside cell

• more positive charge outside attracts negatively charged ions

what is membrane potential a measure of

voltage inside cell compared to the voltage outside the cell

cell membrane potential at rest

• -70mV

• inside of the cell is more negative than the outside

what happens when one sodium channel is open on the cell membrane

• Na from outside enter cell passively

• depolarization occurs

what happens when multiple sodium channel is open on the cell membrane

• a lot of Na travels into the cell passively

• more positive charge on the inside than outside

• hyperpolarization occurs

inside of a cell typically

• negatively charged proteins

• mostly K+ and less Na+

• K+ has a tendency to leave cells

outside of a cell typically

• mostly Na+ and less K+

• Na+ has a tendency to enter cells

cell membrane typically

• has leaky channels

• more K than Na channels

• has the Na/K pump

Na/K pump

• uses ATP at rest

• 3 Na out, 2 K in

• builds Na outside and K inside cells

• creates concentration gradient

• creates the charged environment when needed

what helps maintain the resting potential

• K+ leaky channels 

• Na/K pumps

• chlorine outside the cell balances the organic anions inside the cell

leaky K+ channel

allows passive diffusion of K+

why are neurons excitable

can rapidly change their membrane potential

depolarization

• membrane potential becomes more positive

• more positive charge inside cell

hyperpolarization

• membrane potential becomes more negative

• more negative charge inside

repolarization

membrane returns to resting value

graded potential

• a stimulus produces a change in the membrane potential which proportional to the duration and amplitude of the stimulus

• dissipates down cell body

how does a membrane potential decrease exponentially with distance

1. NT binds to a ligand gated Na+ channel

2. Na+ enters cell through the open channel

3. current spreads through the cell

4. the strength of the signal decreases with distance

what does the magnitude of graded potential depend on

• strength of stimulus

• i.e. the amount of NT

no stimulus graded potential

• no ion channels are open

• resting membrane

small stimulus graded potential

• small [NT] released

• a small number of Na will pass through Na channel

• smaller magnitude 

• results in a small depolarization and hyperpolrization

big stimulus graded potential

• large [NT] released

• a large number of Na will pass through Na channel

• larger magnitude 

• results in a big depolarization and hyperpolrization

stimuli thats not chemical

high/low temp

what determines if the postsynaptic cell has reached the threshold required for an AP

net change in postsynaptic membrane voltage

synaptic summation and the threshold for excitation

act as filter so that random “noise” in the system is not transmitted as important info

inhibitory post-synaptic potentials

• tiny signals

• less likely to fire an AP

• IPSP

excitatory post-synaptic potentials

• more likely to fire an AP

• EPSP

axon hillock

• every neuron has one

• each hillock has a unique threshold for signals

• if met, AP is produced

• overly sensitive

why does it matter that the axon hillock is overly sensitive

• if threshold is not met, the signal is probabaly irrelevant

• threshold here is lower than everywhere else in the body

integration of info

• single neuron may receive info from thousands of synapses (excitatory/inhibitory)

• axon hillock integrates all stimuli

• determines rate of AP generation 

how are action potentials different from graded potentials

• APs are not graded

• u get it or u dont

• looks the same everytime

• summation of graded potentials lead to APs

stimulus for an AP

• Na voltage gated channels opening

• occurs at AP peak

• leads to a lot of Na entering cells

• -70 to 30mV

what happens when neuron reaches 30mV

• Na voltage gates change conformation (not exactly closed)

• enter refractory period

• closes after 3-4 sec ready for next stimulus

• open K volted gated channels

• ton of K leave the cell - repolarization

when does hyperpolarization occur

• cell membranes are permeable to K, therefore hyperpolrization occurs

• AP cannot occur during this

when do Na+ gated channels open

-55mV

how are gated Na channels examples of positive feedback loops

• goal is to reach 30mV

• allows cell to enter refractory period

process of Na+ gated channels opening and closing

1. at resting membrane potential, Na+ channels are closed

2. strong graded potentials causes gate to open, allowing Na+ to enter cell

3. increased [Na] depolarizes cell, opening more Na channels in a positive feedback loop

   1. causes rapid depolarization phase of AP

4. channel “closes” when 30mV is reached

5. repolarization causes channel to return to its original state

propagation of an AP

• as depolarization areas move down the axon, the areas it has already passed starts to enter repolarization

• AP travels unidirectionally

what causes APs to travel unidirectionally

• refractory period

• during this period, depolarization cannot occur in that area

where are the voltage gated channels located

nodes of ranvier

where are nodes of ranvier

at the gaps of myelin sheaths

why does depolarization only occur at nodes of ranvier

• causes AP to jump from node to node along the axon

• faster propagation of AP

• saltatory conduction

what will happen without shwann cells

• no myelin

• signal will be weaker as it travel down axon

• AP will not occur

nodes of ranvier

• saturated with Na, K channels

• AP is reproduced here

synapse

• place where info is transmitted from one neuron to another

• form between axon terminals and dendritic spines

what can synapses connect

• axon to axon

• dendrite to dendrite

• axon to cell body

2 types of synapses

• electrical

• chemical

electrical synapse

direct flow of electrical current from one cell to another

chemical synapse

• secrete NT molecules that activate receptors

• more common

how do electrical synapses work

• pre and postsynaptic membranes are physically connected by channel proteins forming gap junctions

• allow current to pass directly from one cell to next

• allows ions that carry current and large molecules such as ATP to pass through junction pores

• no delay in transmission

• can be bidirectional

• more reliable since less likely to be blocked

how do chemical synapses work

• slower than electrical synapses

• many points of intervention

• not as reliable

how do chemical synapses occur

1. AP arrives at axon terminal

2. voltage gated Ca2+ channels open and Ca2+ enters the axon terminal

3. Ca2+ entry causes NT containing synaptic vesicles to release their contents by exocytosis

4. NT diffuses across the synaptic cleft and binds to ligand gated ion channels on the postsynaptic membrane

5. binding of NT open ligand gated ion channels, resulting in graded potentials

how does a chemical synapse termianate

reuptake by the presynaptic neuron, enzymatic degradation and diffusion reduce NT levels

neurotransmitters

• a chemical compound released by a neuron at a synapse and affects the transmembrane potential of another cell

• bind to receptors

• directly impact membrane potential of postsynaptic cell

neuromodulator

• a chemical compound released by a neuron that adjusts the sensitivities of another neuron to specfiic NTs

• typically neuropeptides such as opioids (endorphins)