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Examples of extracellular fluid
Blood plasma, lymph, CSF, synovial fluid, interstitial fluid
Membrane protein: ion channel
Allows diffusion of ions (passive)
Membrane protein: transporter
Active transport (uses ATP)
Ligand-gated channel
Opens when a chemical (ligand) binds
Voltage-gated channel
Opens in response to a change in membrane potential
Ligand (definition)
Anything that binds a receptor to exert an effect
Membrane potential
Difference in electrical charge across a membrane, in mV
Typical neuron resting membrane potential
About -70 mV (range -40 to -70 mV)
Where is Na+ concentrated at rest?
Outside the cell
Where is K+ concentrated at rest?
Inside the cell
Why does Na+ "want" to enter the cell at rest?
Higher concentration outside AND negative interior
Na+ entering the cell causes
Depolarization (more positive)
K+ leaving the cell causes
Hyperpolarization / repolarization (more negative)
Main contributor to negative charge inside the cell
Large intracellular proteins (anions that can't leave)
3 things that maintain RMP
1) K+ leaks out faster than Na+ leaks in; 2) trapped intracellular anions; 3) Na+/K+ ATPase
Na+/K+ ATPase ratio
3 Na+ out for every 2 K+ in
Why is the Na+/K+ pump electrogenic?
It pumps more cations out than in
Effect on RMP of blocking Na+ leak channels
RMP becomes more negative
Pump moving 2 Na+ out and 4 K+ in would cause
Depolarization (more positive inside)
How is the Na+/K+ pump cycle terminated?
Dissociation of ADP and Pi
Graded potentials (key features)
Short-lived, local changes from ligand-gated channels; can depolarize or hyperpolarize; can be summed
Where do graded potentials mainly occur?
Dendrites (and cell body)
Depolarizing graded potential is caused by
Ligand-gated Na+ channels opening (Na+ in)
Hyperpolarizing graded potential is caused by
Ligand-gated K+ channels opening (K+ out)
Spatial summation
Graded potentials summed because they are close in location
Temporal summation
Graded potentials summed because they are close in time
Conditions for summation of graded potentials
Close in space OR time
Graded potentials return to RMP via ___ feedback; APs are propelled by ___ feedback
Negative; positive
Threshold for an action potential
About -55 mV
Where are action potentials initiated?
Axon hillock (trigger zone)
Which cells can have action potentials?
Excitable cells: neurons (axon) and muscle
"All-or-nothing" means
An AP either fires fully or not at all; amplitude is always the same
Can action potentials be summed?
No
Action potential feedback type
Positive feedback (Na+ entry opens more voltage-gated Na+ channels)
AP resting phase: channels
All voltage-gated channels closed
AP depolarizing phase
Voltage-gated Na+ channels open → Na+ influx
AP repolarizing phase
Voltage-gated K+ channels open and Na+ channels close → K+ efflux
AP hyperpolarizing phase
Voltage-gated K+ channels still open (delayed closing) → dips below RMP
What causes the hyperpolarization (undershoot) phase?
Delayed closing of K+ channels
Order of AP phases
Resting → depolarizing → repolarizing → hyperpolarizing → resting
Absolute refractory period
During depolarization + repolarization; NO new AP possible
Relative refractory period
During hyperpolarization; new AP possible but needs a bigger stimulus
Purpose of the refractory period
Prevents backward propagation (one-way conduction), keeps APs discrete, lets the cell recover
What determines the strength of a nerve signal?
Frequency of action potentials
Blocking voltage-gated K+ channels would NOT change
The depolarization phase
If voltage-gated K+ channels didn't open
APs would not be followed by a wave of repolarization
An action potential is terminated by
Efflux of K+
Is an AP propagated by ligand-gated channels?
No - by voltage-gated channels
Conduction (propagation)
Movement of an impulse down an axon
Transmission (neurotransmission)
Movement of a signal across a synapse to another cell
Electrical synapse
Gap junctions directly connect cells; very fast; synchronizes cells
Locations of electrical synapses
Cardiac muscle (myocardium), smooth muscle (GI, uterus/myometrium), parts of the brain
Where are electrical synapses NOT found?
Skeletal muscle
Chemical synapse
Neurotransmitter crosses a synaptic cleft to bind receptors on the postsynaptic cell
What triggers NT release at the axon terminal?
Influx of Ca2+ through voltage-gated Ca2+ channels
Steps of a chemical synapse
AP arrives → voltage-gated Ca2+ opens → Ca2+ in → vesicles release NT → NT binds postsynaptic receptors → ligand-gated channels open → graded potential → AP if threshold reached
Axon terminals are filled with
Vesicles (containing neurotransmitter)
EPSP
Excitatory postsynaptic potential: depolarizes, moves cell toward threshold, can be summed
IPSP
Inhibitory postsynaptic potential: hyperpolarizes, moves cell away from threshold
More excitatory than inhibitory input but below threshold results in
An EPSP (no AP)
Lambert-Eaton syndrome effect
Presynaptic voltage-gated Ca2+ channels inactivated → NT not released
Are all neurotransmitters excitatory?
No
Catecholamines
Dopamine, norepinephrine (noradrenaline), epinephrine (adrenaline)
Is serotonin a catecholamine?
No
Serotonin is associated with
Sleep, dreaming, mood, nausea/vomiting
Neurotransmitter associated with allergic reactions
Histamine
Excitatory amino acid neurotransmitters
Glutamate and aspartate
Inhibitory neurotransmitters
GABA and glycine
Peptide NT involved in pain
Substance P
Peptide that stimulates uterine contraction and milk expression
Oxytocin
Enkephalins / endorphins
Opioid-like peptides that inhibit pain
Is histamine a peptide neurotransmitter?
No (it's a biogenic amine)
Inactivation (NT removal)
Enzyme breaks down the NT (e.g. acetylcholinesterase breaks down ACh)
Reuptake (NT removal)
NT taken back into the presynaptic neuron
Main removal method for catecholamines
Reuptake
SSRIs (e.g. fluoxetine)
Block serotonin reuptake → more serotonin in the synapse
Atropine
Blocks ACh receptors → decreases neurotransmission
What increases ACh levels in a cholinergic synapse?
More presynaptic action potentials
Increase in synaptic ACh → ___ neurotransmission
Increase
MAO inhibitors would NOT affect which NT?
Acetylcholine
Electromyography (EMG)
Measures electrical activity in muscle
Latency (EMG)
Delay between stimulation and contraction; used to calculate conduction velocity
Tetany
Prolonged contraction of skeletal muscle due to electrical stimulation
Why does the "death grip" occur?
Forearm flexors are stronger than extensors
Membrane protein: receptor
Binds signals (interaction)
Membrane protein: enzyme
Catalyzes reactions
Membrane protein: anchor
Structural stability
Membrane protein: identity marker
Immune recognition
Three stimuli that open gated channels
Chemical (ligand), electrical (voltage), mechanical
Intracellular fluid (ICF)
Fluid inside cells (cytosol); depends on precise regulation of ECF
What do blood, urine and CSF tests really measure?
Homeostasis (composition of extracellular fluid)
Why is one-way conduction especially important in the heart and GI tract?
They need unidirectional, progressive contraction
Duration and spread of a graded potential
About 10 ms; only a few microns along the membrane