Week 8 Physiology (Lecture 1)

graded/action potentials similarities

both driven by opening ion channels

• Na+ channels opening…depolarization (more positive)

• K+ channels opening…hyperpolarization (more negative)

neither graded/action potentials can drive membrane potential beyond relevant equilibrium potentials

• Na+: +60 mV

• K+: -90 mV

• have to be somewhere between these two

graded potentials

produced by different stimuli:

• physical

• chemical

• taste

• odorants

• vibrations

• electromagnetic radiation (light)

  • these stimuli change the membrane potential of sensory cells

all special sensory cells use graded potentials

usually: stimulus…depolarizing graded potential…exocytosis of neurotransmitters

• vision is the exception

  • photoreceptors are depolarized in absence of light

  • photoreceptors are hyperpolarized if light stimulus occurs

• both: depolarization leads to neurotransmitter release

graded potentials lead to action potentials (location)

graded potentials: at input end

action potentials: along axon

• neurotransmitter released by a sensory cell can either cause:

  • excitatory effect: depolarization

  • inhibitory effect: hyperpolarization

for action potential to occur:

• graded potential…depolarizes axon hillock…reaches threshold (-55 mV)

• axon hillock must go from -70 mV to at least -55 mV

  • voltage-gated Na+ channels open & action potentials occur

duration of graded/action potentials

graded: can last as long as stimulus is present

• can have variable durations

action: brief

• follows normal sequence & returns toward resting membrane potential

amplitude of graded/action potentials

graded: variable amplitude

• weak stimulus…weak depolarization…less neurotransmitter release

• strong stimulus…strong depolarization…more neurotransmitter release

action: same amplitude

• once threshold is reached, same amplitude every time

• “all-or-none” principle

• stronger stimulus causes more action potentials per unit of time

refractory period

after action potential, voltage-gated Na+ channels need to reset before another action potential can occur

absolute refractory period

• Na+ channels are open or inactivated

• another action potential can’t be regenerated

relative refractory period

• during hyperpolarization, enough Na+ channels have reset

• another action potential can occur

• but, membrane is more negative than normal so stronger stimulus is needed to reach threshold

• as membrane becomes more negative, more Na+ channels reset, easier to generate another action potential

action potential frequency

stronger stimulus doesn’t make action potential bigger

stronger stimulus…stronger depolarization…higher frequency of action potentials

Graded Potentials: info encoded by amplitude & duration

Action Potentials: info encoded by frequency

signal transmission

stimulus→graded potential→action potential→neurotransmitter release

strong stimulus→stronger depolarization graded potential→higher frequency of action potentials→more neurotransmitter release (this is how info transmits rapidly along neuron)

synapse

specialized, short-distance connection between presynaptic cell & postsynaptic cell

• presynaptic cell releases signal

• postsynaptic cell receives signal

synaptic cleft: fluid-filled space between pre and postsynaptic cells

• presynaptic neuron:

  • conducts impulse toward synapse

  • synaptic vesicles

  • store neurotransmitter

• postsynaptic neuron:

  • neurotransmitter receptors

neurotransmitter release at the axon terminal

action potential travels down the axon

when it reaches axon terminal:

• action potential arrives at axon terminal

• depolarization

• voltage gated Ca²+ channels open

• Ca²+ enters axon terminal

• causes vesicles to fuse w/ plasma membrane

• exocytosis

• neurotransmitter released

• neurotransmitter binds receptors on next cell

Ca²+ and neurotransmitter release

neurotransmitter release is Ca²+ dependent

rise in intracellular Ca²+ causes:

• vesicular & target snares to interact

• exocytosis of neurotransmitters

  • allows vesicle to fuse w/ membrane

more action potential frequency…more neurotransmitter released

clearing Ca²+ after neurotransmitter release

after neurotransmitter release, cells needs to lower intracellular Ca²+

• Ca²+ ATPase:

  • uses primary active transport

  • uses ATP

  • pumps Ca²+ out of the cell against its concentration gradient

• Na+/Ca²+ Exchanger:

  • uses secondary active transport

  • uses Na+ gradient to help move Ca²+ out

  • exchanger is faster than Ca²+ ATPase

goal: bring intracellular Ca²+ back to 0.001 mM/100 nM

• stops neurotransmitter release

removing neurotransmitter from synapse

diffusion

• slow process

enzymatic breakdown

• breaks neurotransmitter into another substance

• once broken down, can’t activate receptor

• fastest way

vesicle recycling/endocytosis

• let vesicle fuse, exocytosis (get signal in), endocytosis

• vesicle: recycled, refilled w/ neurotransmitter, used again

resetting the neuron

after action potential, neuron must restore:

• ion concentration

• membrane potential

• Ca²+ levels

• neurotransmitter levels

*ion channels help bring membrane potential back toward resting conditions

Na+/K+ ATPase: 3 Na+ out, 2 K+ in

neurons need recovery time: ion concentrations become off balance

• neuronal fatigue

• replenished by sleep (resets ion concentration, clear metabolites, recover)

excitatory vs. inhibitory postsynaptic potentials

when neurotransmitter reaches the next cell, it can cause either:

• Excitatory Postsynaptic Potential: causes depolarization (more likely to reach threshold)

• Inhibitory Postsynaptic Potential: causes hyperpolarization (less likely to reach threshold)

Which ion causes Excitation or Inhibition?

Na+ enters (depolarizes, excitatory)

Ca²+ enters (depolarize, excitatory)

K+ leaves (hyperpolarize, inhibitory)

Cl- enters (hyperpolarize, inhibitory)

*neurotransmitter effect depends on which receptor it binds to & what ion channel the receptor controls

summation

multiple graded potentials can combine together

temporal summation

• multiple signals come from same axon close together in time

• Ex.: 2nd excitatory postsynaptic potential arrives before 1st disappeared…adds to it

spatial summation

• signals come from different locations/neurons at approximately same time

multiple excitatory inputs can add together

inhibitory input can counteract with excitatory input

action potentials are started ONLY

if excitatory postsynaptic potentials dominate & bring membrane potential to threshold

Graded Potentials

activated channel: ligand-gated, or chemical, or physical stimulus

amplitude: varies w/ initiating event

amplitude w/ distance: decreases w/ distance from activation

duration: varies w/ initiating event

electrical polarity: depolarizing (excitatory), hyperpolarizing (inhibitory)

threshold: none

refractory period: none

can be summed?: yes

Action Potentials

activated channel: voltage-gated channels

amplitude: all-or-none

amplitude w/ distance: remains the same at each point along axon

duration: consistent & brief

electrical polarity: only depolarizing (excitatory)

threshold: less negative than -55 mV

refractory period: yes

can be summed?: no

conduction velocity

depends on:

• axon diameter

  • larger axon, lower internal resistance, faster electrical conduction

• degree of myelination

  • our axons are very small, we rely on myelin (electrical insulation around axon)

without myelin:

• electrical current can leak out through membrane

• signal loses strength

• conduction is slower

with myelin:

• current travels farther in axon

• less current leaks out

• action potentials travel much faster

nodes of ranvier

gaps in myelin

voltage-gated Na+ channels are concentrated at the gaps in myelin

signal jumps from node to node instead of generating action potential continuously

• saltatory conduction…faster action potential propagation

• myelination speeds conduction by 30x

multiple sclerosis

myelin in nervous system becomes damaged

without proper myelin:

• electrical current leaks out

• action potential propagation becomes impaired

• neural signals may not reach destinations properly

causes problems with:

• muscle control

• standing/walking

• vision & speech

nervous/endocrine system

nervous system: action potential…neurotransmitter…nearby cell

endocrine system: hormone…bloodstream…target cell

neurohormones

some neurons release chemical signals into bloodstream

• can function as hormones

neurons participate in both nervous system signaling & endocrine signaling

neurotransmitters vs. hormones

neurotransmitters

• released from vesicles

• released via exocytosis

• acts as synapses

• generally short-distance signaling

hormones

• released through exocytosis

• not ALL are stored in vesicles

  • steroid hormones

hydrophilic hormones

can’t easily cross lipid membrane

hormone stays outside cells

binds to receptor on cell surface

Ex.: peptide hormones, protein hormones, modified amino-acid proteins

hydrophobic hormones

can cross plasma membrane

diffuses out of producing cell

travels to target

diffuses into target cell

binds intracellular receptor

Ex.: steroid hormones, T3, T4

• T3 & T4 are amino acid derived hormones, because they’re hydrophobic, they act like steroids

2 major hormone categories

amino-acid-based hormones (hydrophilic)

• modified amino acids

• peptides (chains of amino acids)

• protein (longer chains of amino acids)

steroid hormones (hydrophobic)

• made of cholesterol

endocrine system glands

primary job: release hormone + signal other cells

pineal gland

hypothalamus

pituitary gland

thyroid gland

parathyroid gland

adrenal glands

pancreas

ovary (female)

testis (male)

*about 30 hormones

• ½ control release of other hormones

Amino-Acid Based Hormones vs. Steroid Hormones: notes

Hydrophilic (amino-acid based):

• tyrosine (epinephrine, norepinephrine, dopamine, T3, T4)

  • T3 & T4 have cofactor iodine…act like steroids

• tryptophan (melatonin)

Hydrophobic (steroids):

• adrenal cortex (aldosterone, cortisol, androgens)

• gonads (estrogen, progesterone, testosterone)

Amino-Acid Based Hormones vs. Steroid Hormones: construction

Hydrophilic (amino-acid based):

• transcription in nucleus

• translation on rough ER

Hydrophobic (steroids):

• construction by smooth ER

Amino-Acid Based Hormones vs. Steroid Hormones: storage

Hydrophilic (amino-acid based):

• in vesicles

Hydrophobic (steroids):

• no storage; made when needed

Amino-Acid Based Hormones vs. Steroid Hormones: release

Hydrophilic (amino-acid based):

• exocytosis

Hydrophobic (steroids):

• simple diffusion through plasma membrane

Amino-Acid Based Hormones vs. Steroid Hormones: blood transport

Hydrophilic (amino-acid based):

• water soluble, free in plasma

Hydrophobic (steroids):

• hydrophobic, rides on plasma proteins (albumin, globulins)

Amino-Acid Based Hormones vs. Steroid Hormones: duration in blood

Hydrophilic (amino-acid based):

• short lived, removed by kidney or liver

Hydrophobic (steroids):

• long lived, protected from kidney & liver as they’re attached to plasma proteins

Amino-Acid Based Hormones vs. Steroid Hormones: receptor location

Hydrophilic (amino-acid based):

• surface of cells

Hydrophobic (steroids):

• intracellular-cytosol or nucleus