Principles of Neural Communication Flashcards
Which cell types have a membrane potential?
- all cells have a membrane potential!
- only nerve cells and muscle cells, however, have developed a way to utilize the potential
What is the resting potential of a cell? What is the threshold potential needed to initiate an action potential? What is the peak potential reached during an action potential?
- resting: -70 mV
- threshold: -55 to -50 mV
- peak: +30 to +40 mV
Leak Channels vs. Gated Channels
- leak: always open, permitting unregulated movement of a specific ion
- gated: opens in response to a particular stimulus (voltage, chemical, mechanical, thermal)
- (don’t forget cells also have Na+-K+-ATPase pumps that pump these ions against their gradients)
Graded Potentials vs. Action Potentials
- graded: small (10-20 mV) short-distance signals that can initiate an action potential; decrease in strength as they spread outward from the initial source; can be of varying magnitude; no refractory periods
- action: large (100 mV) long-distance signals; do not decrease in strength as they spread - they are continuously propagated along; all-or-nothing (always the same magnitude or nothing); refractory periods
Which ion is the greatest contributor to the resting potential? Why?
- K+
- the concentration of K+ is greater inside the cell than outside, while that of Na+ is greater outside; however, at resting potential, the cells is about 100x more permeable to K+ than Na+, so a net movement of K+ OUT of the cell (via K+ leak channels) occurs and generates the negative resting potential
What is the structure of the voltage gated Na+ channels? What are the three conformations of these channels?
- voltage gated Na+ channels have 2 gates: an activation gate in the middle of the channel and an inactivation gate at the cytoplasmic end
- 1) closed active (can be opened): activation gate closed, inactivation gate open
- 2) open: both gates open
- 3) closed inactive (can’t be opened for a while): activation gate open, inactivation gate closed
Explain what happens to ion channels during the resting, depolarization, and repolarization stages.
- (leak channels and ATPase pump are always open/working)
- resting: voltage gated Na+ channels are closed active, voltage gated K+ channels are closed
- initial depolarization: some voltage Na+ channels open, adding to the depolarization
- threshold: explosive inflow of Na+ due to large amounts of voltage Na+ channels opening; these are then rapidly closed (closed inactive)
- repolarization: voltage gated K+ channels open slowly and then close slowly (results in a slight hyperpolarized state)
- resting: voltage gated K+ channels are closed and voltage gated Na+ channels switch to closed active
Very soon after the threshold potential and action potential are generated, voltage gated Na+ channels are rapidly closed - what mechanism drives this closing?
- the voltage event that triggers these channels to open actually also induces them to close, but at a much slower rate
- the event triggers the rapid-opening of the activation gates and the slow-closing of the inactivation gates (when the peak potential is reached, the inactivation gates will finish closing)
What’s the role of the Na+-K+-ATPase pumps?
- these pumps gradually restore the concentration gradients of Na+ and K+ back to normal after an action potential occurs
- they therefore help generate the resting potential (along with leak channels)
- (note that the concentrations do not need to be fully restored to normal in order for another action potential to be generated because there is still way more K+ inside and Na+ outside)
Where are graded potentials and action potentials generated in the neuron? What determines whether a particular part of the cell will generate a graded vs. action potential?
- graded potentials are generated in the dendrites and cell body
- action potentials are generated in the axon
- areas that generate graded potentials simply have fewer voltage gated Na+ channels
Absolute and Relative Refractory Periods
- absolute refractory period: once an area generates an action potential, it can’t generate another one until resting potential is reached
- relative refractory period: a period following the absolute refractory period (so once resting potential is reached) that requires a stronger signal than the initial triggering event in order to generate another action potential
How do action potentials convey the strength of a stimulus?
- stimulus strength is coded by the FREQUENCY of action potentials; action potentials are all-or-nothing, meaning that they don’t come in varying amplitudes
- (graded potentials convey stimulus strength with amplitude magnitude)
Contiguous vs. Saltatory Conduction
- contiguous conduction occurs in unmyelinated axons
- saltatory conduction occurs in myelinated axons (about 50x faster); the lipid sheath acts as an insulator that prevents current/ion leak, “forcing” the current to jump along the nodes of Ranvier = faster conduction
Which parts of the neuron has the largest concentrations of voltage gated Na+ channels?
- the axon hillock (this is why the action potential is generated here)
- in a myelinated axon, the nodes of Ranvier also have very high concentrations of these channels (the actual myelinated parts have very few)
Why do axons with larger diameters have increased conduction speeds?
- larger diameter means less resistance!
Which channels are involved in triggering neurotransmitter exocytosis? Which channels on the post-synaptic cell respond to the neurotransmitters?
- voltage gated Ca2+ channels open via the action potential to trigger neurotransmitter exocytosis (via Ca2+ influx)
- chemically gated channels on the post-synaptic cell open in response to the neurotransmitter
EPSPs, IPSPs, and GPSP
- these are graded potentials that provide input to a neuron, determining whether or not an action potential will be generated
- EPSP: excitatory postsynaptic potential; increase permeability of Na+ and K+ to induce small depolarizations
- IPSP: inhibitory postsynaptic potential; increase permeability of K+ and Cl- to induce small hyperpolarizations
- GPSP: grand postsynaptic potential
Increasing the permeability of K+ will result in an inhibiting hyperpolarization, which is how IPSPs work, but EPSPs also increase the permeability of K+, so how do they result in depolarization?
- (increasing K+ permeability will result in K+ moving OUT of the cell, thus causing hyperpolarization)
- EPSPs increase permeability of both K+ and Na+, but the movement of Na+ in exceeds that of K+ out because the electrical and the chemical gradient of Na+ favor its movement in, while only the chemical gradient of Ca2+ favors its movement out; results in a net depolarization
What are neuropeptides? What type of vesicles are they packed into?
- neuropeptides are larger molecules that are also released with the classic neurotransmitters
- they tend to bring about slower, more prolonged modulating responses
- they are packaged into large dense-core vesicles (vs. the small synaptic vesicles of classic neurotransmitters)
What are the three ways communication between cells via extracellular (primary) messengers can occur?
- 1) opening/closing of chemically gated ion channels (the receptor is the channel): fast; most neurotransmitters
- 2) activating receptor-enzymes (the receptor is an enzyme): slow; tyrosine kinase pathway
- 3) activating secondary messengers via GPCRS: slow; most common pathway in general
Will ions with a Nernst potential positive to the Em cause depolarization or hyperpolarization? What about those with a Nernst potential negative to the Em?
- positive Nernst (Na+): depolarization
- negative Nernst (K+ and Cl-): hyperpolarization
What is the classification scheme of nerve fibers that pertain to both sensory and motor fibers?
- Aalpha (largest, myelinated): fastest
- Abeta > Agamma > Adelta
- B
- C (smallest, unmeylinated): slowest
What is the classification scheme of nerve fibers that pertain only to sensory fibers?
- I (largest, myelinated): fastest
- II
- III
- IV (smallest, unmyelinated): slowest
What are decussations?
- decussations are areas of the CNS where sensory and motor pathways from one side of the body cross over to the contralateral side
Which fibers run through the dorsal roots of the spinal cord? The ventral roots?
- dorsal roots contain primary afferent neurons (cell bodies lie in the dorsal root ganglia)
- ventral roots contain efferent neurons (cell bodies lies in the grey matter of the spine)
What role do astrocytes play in neurotransmission?
- astrocytes take up the NT upon its release to help stop the signal
- in terms of glutamate and GABA, astrocytes take them up and convert them to glutamine before returning them to the neurons (where it will be remade into glutamate or GABA)
What are the two most common neurotransmitters used in the CNS? Which neurotransmitter is the most common in the PNS?
- glutamate (excitatory): used by about 70% of the cortical terminals
- GABA (gamma-aminobutyric acid, inhibitory): used by about 20% of the cortical terminals
- in the PNS, acetylcholine is the most common NT
What is the GABA equivalent used in the spinal cord?
- glycine
How are glutamate and GABA synthesized? What about aspartate?
- all three are made from metabolic shunts in the TCA cycle
- alpha-ketoglutarate forms glutamate
- from gulatamte, GABA is made (GABA can be formed into succinate, returning to the TCA cycle)
- asparate is formed from oxaloacetate
Which exogenous chemicals interact with GABA receptors?
- tranquilizers (benzos), alcohol, and barbituates
What are the three major catecholamines? From which amino acid are they derived?
- dopamine, norepinephrine, and epinephrine
- they are derived from tyrosine (the same pathway as melatonin)
What type of receptors are dopamine receptors? Which exogenous chemicals block the re-uptake of dopamine?
- DA receptors are GPCRs; D1 receptors increase cAMP and D2 receptors decrease cAMP (D2 agonists treat Parkinsonism, D2 antagonists are anti-psychotics)
- cocaine and amphetamines block DA re-uptake
Which amino acid is serotonin derived from? What functions is this neurotransmitter involved in?
- derived from tryptophan
- involved with memory, anxiety, depression, diurnal rhythm, and appetite
- in the GIT, serotonin is an emetic
In general, which type of secretory vesicles are involved in the fast release of neurotransmitters? Slow release?
- fast release: small, clear vesicles
- slow release: large, dense vesicles
Compare hormones and neurotransmitters.
- neurotransmitters: more rapid release, fast action, short-distance (not including the axons) low affinity receptors, rapid re-uptake
- hormones: slow release, slower and longer action, long distance, very high affinity receptors, little/no re-uptake
What does an inverse agonist do to a receptor?
- inverse agonists lower the basal activity of a receptor
LGICs are also known as what? What about GPCRs? Can a specific neurotransmitter bind to both types of receptors?
- LGICs (ligand gated ion channels) are ionotropic receptors
- GPCRs (G-protein coupled receptors) are metabotropic receptors
- many NTs have both types of receptors:
- glutamate: GluR (LGIC) and mGluR (GPCR)
- GABA: GABAa (LGIC) and GABAb (GPCR)
- ACh: nAChR (LGIC) and mAChR (GPCR)
- serotonin: 5HT3 (LGIC) and other numbered 5HT (GPCR)
Channels involved in neurotransmitter re-uptake use what mechanism? Which channel re-uptakes ACh?
- all use Na+ coupling
- some also use K+, and others also use Cl-
- ACh is NOT taken back up - instead, it is destroyed by acetylcholine esterase
What is unique about glial cells that prevents them from generating action potentials?
- these have very high membrane potentials (-80 mV) as opposed to the neurons’ -50 mV