Chapters 6,7

membrane potential

the difference in electrical potential between the interior and the exterior of a cell

threshold potential

the membrane potential to which a membrane must be depolarized to initiate an action potential (-40 - -55 mV)

voltage/electric potential difference

potential difference between two points

current

the flow of electric charge through a medium; carried by moving ions to neurons

resting potential

the membrane potential of quiescent cellls (-70 - -90mV)

• 3 Na+ OUT 2 K+ IN

• K+ and Na+ channels have passive ion leakage down concentration gradients

Hodgkin and Huxley

the first two researchers to record an action potential with the use of a squid giant axon

1. Axon was dissected from a squid and an electrode was inserted within it and connected to an amplifier

2. Trace shows change in voltage during an action potential

3. Cell voltage is measured in milivolts; resting potential of a squid axon is -76 mV

Equilibrium Potential

the potential at which the electrostatic force in the cell is exactly equal to the force of diffusion for an ionic species; the forces of K+ and Na+ channels are atractive at 102mV

Nersnt Equation

equilibrium potential for an individual ion

Ek = 61.5 log10 (3 mM/135mM) = -
102mV

Goldman equation

equilibrum potential across a cell’s membrane for all permanent ions

voltage clamp

measures the ion currents across the membrane and holds the voltage at a set level; researchers can inject current into the cell to maintain a certain voltage

Ohm’s Law

V = IR

physiological changes at single-channel levels

voltage: ~100mV

resistant: drops ~100x as channels open

current: ~10 nanoamperes caused by Na+ influx and K+ efflux

concentration: ~0.1 picomoles of Na+ enter and ~0.1 picomoles of K+ leave

capacitance: low

scorpion toxin (ScTX) and puffer fish/terodotoxin (TTX)

block Na+ channels, revealing K+ currents

voltage-gated sodium channels

S4 subdomain of the alpha subunit detects voltage changes via positively charged arginine residues

tetraethylamonium (TEA)

blocks K+ channels, revealing Na+ currents

epilepsy

millions of neurons release K+ simultaneously, causing a positive shift in the K+ equilibrium and resting potential

• causes hightened neuron sensitivity

• spreading depolarization waves inducing seizures

• interictal epileptiform discharges (IEDs) are hypersynchronous patterns of brain activity

electroencephalogram (EEG)

transcranial measurement using 64 silver electrodes to record millions of postsynaptic electrical currents in mV over time

Neurotransmitter Criteria

1. Synthesized by and released from neurons

2. Released from nerve terminals in chemically identifiable forms

3. A reproducible response at the postsynaptic cell

4. Effect blocked if appropriate receptor antagonist is used

5. Mechanisms of termination present

glutamate

receptor: AMPA

location: hippocampus

function: memory

GABA

receptor: GABA-A

location: cerebellum

function: inhibition

acetylcholine

receptor: nicotinic

location: cortex

function: attention

dopamine

receptor: D1

location: striatum

function: movement

noradrenaline

receptor: alpha-2

location: cortex

function: attention

adrenaline

receptor: beta

location: brainstem

function: arousal

serotonin

receptor: 5-HT1A

location: hippocampus

function: mood

endorphin

receptor: micro-opiod

location: hypothalamus

function: analgesia (pain relief)

Neurotransmitter life cycle

1-3. Amino acid precursor accumulates in neuron, is metabolizd, and packaged in vesicles

4-5. transmitter is released into synaptic cleft, interacting with autoreceptors or regulating post-synaptic receptors

6. high-affinity transporters terminate neurotransmitter action

7. transmitter diffuses away from the synaptic cleft

8. glia and auto-transporters take in transmitter through membrane-bound transporters

GABA transmitter life cycle

1. GABA is converted into glutamate by GABA transaminase (GABA-T); glutamine synthase then produces glutamine

2. glutamine enters neuron and is transformed by glutaminase into glutamate; GABA is formed from glutamate by glutamic acid decarboxylase (GAD)

3. released GABA is accumulated by GABA transporters (GAT) in astrocyte glia

4. Caffeine inhibits GABA release; alcohol and xanax increase GABA activity

GABA

dervied from glucose metabolism; major inhibitory transmitter of the brain, opening channels to hyperpolarize neurons

transmitter life cycle in catecholamine neurons

1. tyrosine is accumulated by the neuron

2. it is later metabolized to L-DOPA by tyrosine hydroxylase (TH) and L-aromatic amino acid decarboxylase (L-AADC) to dopamine (DA)

3. Dopamine is taken into vesicles (final step in dopaminergic neurons)

4. in norepinephrin (NE) neurons, dopamine is converted to norepinephrine by dopamine-beta-hydroxylase (DBH) inside vesicles

5. accumulation by NE transporter (NET) facilitates its breakdown to inactive dihydroxyphenylglycine (DHPG) by monoamine oxidase (MAO)

welbutrin

inhibits dopamine and norepinephrin reuptake

prozac

inhibits the serotonin transporter SERT); selective serotonin reuptake inhibitor (SSRI)

functional magnetic resonance imaging (fMRI)

directs blood oxygenation changes occurring in response to neural activity

depression effects

• decreased global neural activity

• decreased hippocampal size

• reduced dendritic branching and spinal density