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58 Cards in this Set
- Front
- Back
What are the bioelectric properties of nerve cells?
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- Phospholipid membranes are essentially impermeable to ions
- Protein families provide function of allowing ion passage across the membrane |
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What are some protein families that allow ion passage across the membrane?
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- ATPase driven pumps
- Transporters - Ion channels - ion movement is allowed following conc. gradient |
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What are some general features of ion channels?
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- Integral membrane proteins
- Multiple membrane spanning domains - Form a hydrophilic channel in the center - Highly evolved to be selective for ions and to be regulated by changes in the cellular environment - Made of multiple subunits that are separate gene products - Glycosylated on extracellular side - Kinase consensus sequences on intracellular side - regulated by intracellular signaling - Specificity for ions that flow through |
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How can ion channels be classified based on gating mechanism?
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- Passive - non-gated, always open (aka pores)
- Active - some mechanism exists for regulation of open/closed states - Leak - open at resting membrane potential |
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How can active ion channels be gated/opened?
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- Membrane potential difference (voltage gated)
- Small extracellular molecules (e.g., neurotransmitters) - Other membrane proteins (e.g., beta-gamma subunits of G proteins) - Intracellular molecules (e.g., ions, ATP) |
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What is the difference between passive ion channels and leak ion channels?
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- Leak channels can be either active or passive
- Leak channels are open at resting potential, passive channels are always open - All passive channels are leak channels, but not all leak channels are passive |
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What is an example of a leak channel?
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K+ channels
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What factors contribute to there being a potential difference across a membrane of excitable cells?
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- Most intracellular proteins are anions - trapped in the cell
- Leak channels in membrane allow movement of K+ and Cl- across membrane - Conductance (g) of membrane for K is 20x greater than conductance for Na * Leads to an unequal distribution of Cl, K, and Na across the membrane |
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What does it mean that the conductance of K+ is 20x greater than it is for Na+?
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There are 20x more K+ leak channels open than there are Na+ leak channels
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What does the Nernst potential represent?
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- Membrane potential at which the ion is in electrochemical equilibrium across the membrane
- Aka: reversal potential because it is the potential at which ion flow reverses |
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What is the resting potential in neurons?
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Em (or Vm) = -60 mV
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What is the Nernst potential for K+?
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Ek+ = -75 mV
(lots inside and less outside cell) (almost always flowing out to try to make Em decrease) |
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What is the Nernst potential for Na+?
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Ena+ = +55 mV
(lots outside and less inside cell) (flows in to try to increase Em) |
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What is the Nernst potential for Cl-?
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Ecl- = -69 mV
(lots outside and less inside cell) (flows in to make Em decrease) |
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What is the relative distribution of Na+, K+, and Cl-?
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- Na+ is high outside and low inside despite wanting to enter the cell (not enough leak channels open)
- Cl- is high outside and low inside because of high negative charge inside cell and open leak channels - K+ is high inside and low outside because of high negative charge inside cell and open leak channels |
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What opposes the K+/Na+ leak across the membrane?
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Na+/K+ ATPase pump - moves Na+ out and K+ in to cell
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What causes an Action Potential to occur?
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- Local depolarization
- Voltage-gated Na+ channels open - Increase I_Na - More depolarization - Etc. |
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What is the equation for current (I)?
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I = V/R (or V=IR)
R is the opposite of conductance |
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How does an Action Potential end?
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- Na+ channels close quickly to decrease conductance of Na+
- K+ channels open slowly (and close slowly) which increases conductance of K+ - Both work to repolarize cell |
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What are the characteristics of an AP? Amplitude, duration?
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- All or none
- 100 mV in amplitude - 1-10 msec in duration - Propagated down axon through cycles of depolarization and repolarization |
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What is the functions and characteristics of a synaptic potential?
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- Mechanism by which the initial change in membrane potential occurs, to begin an AP
- Graded and small (only a few mV) - Local - don't propagate - Able to summate (spatially and temporally) |
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What are the types of summation of synaptic potentials and what do they mean?
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- Spatial summation - many synaptic potentials in one location add up
- Temporal summation - same receptor activated in short amount of time |
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What are the two types of synaptic potentials?
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- Excitatory Postsynaptic Potential (EPSP) - membrane potential moves to more positive value
- Inhibitor Postsynaptic Potential (IPSP) - membrane potential moves to more negative value |
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What are the two mechanisms by which an Excitatory Postsynaptic Potential (EPSP) can occur?
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- Increased conductance - open a ligand gated channel for Na+ or Ca2+
- Decreased conductance - close a channel that is open at resting membrane potential (leak channel, K+) - slower onset changes that last longer |
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What are some examples of increased conductance mediating an Excitatory Postsynaptic Potential (EPSP)?
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- Nicotinic cholinergic receptor
- Several types of glutamate receptors |
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How do you decrease conductance to mediate an Excitatory Postsynaptic Potential (EPSP)?
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- Close a leak channel for K+
- Usually due to changes in phosphorylation of the channel (PKA) --> closure - Regulated by second messenger cascades; G protein coupled receptors (Gs) |
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What is the mechanism by which an Inhibitory Postsynaptic Potential (IPSP) can occur?
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Increased conductance of membrane to K+ or Cl-
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How do you increase the conductance to K+ or Cl- for mediating an inhibitory post-synatpic potential (IPSP)?
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- Open ligand gated Cl- channel (GABA receptor)
- Open K+ channels via direct interaction with G protein - Open K+ channels as a result of changes in the phosphorylation state of K+ channels that are closed |
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Resting Potential:
- Channel specificity - Gating mechanism - Properties |
- Non-gated K+ and Cl- channels, some non-gated Na+ channels (20:1 ratio)
- No gating mechanism - Usually steady, from -35 to -70 mV |
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Action Potential:
- Channel specificity - Gating mechanism - Properties |
- Independently gated Na+ and K+ channels
- Voltage gated - All or none, 100 mV in amplitude, 1-10 msec in duration |
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Increased Conductance EPSP:
- Channel specificity - Gating mechanism - Properties |
- Non-voltage-gated channels; nonselective for univalent cations (K+ and Na+)
- Chemically gated (extracellular binding site) - Graded, fast, several msec in duration, several mV in amplitude |
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Increased Conductance IPSP:
- Channel specificity - Gating mechanism - Properties |
- Non-voltage gated channels for K+ or Cl-
- Chemically gated (extracellular binding site) - Graded, fast, several msec in duration, several mV in amplitude |
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Decreased Conductance IPSP:
- Channel specificity - Gating mechanism - Properties |
- K+ leak channels
- Chemically gated (GPCR, second messenger) - Graded, fast, several msec in duration, several mV in amplitude |
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What are the three types of signaling molecules in the brain?
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- Neurotransmitters
- Neuromodulators - Hormones |
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What are the properties of a neurotransmitter?
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- Works at synapse
- Fast onset and offset effect |
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What are the properties of a neuromodulator?
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- Non-synaptic
- Slower changes - Not responsible for the primary communication between neurons |
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What are the properties of a hormone?
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- Wide distribution
- Great distance between transmitting and receiving cells |
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What are the criteria that must be established for a molecule to be considered a neurotransmitter?
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- Mechanism for synthesis and degradation
- Demonstration of release from neuron following AP - Mimicry by exogenously administered chemical |
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What are the requirements of NT signaling at the Neuromuscular Junction?
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- Fast onset and offset signaling
- High fidelity (happens every time, only when signaled) - Synaptic signaling (ACh in mammals) |
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What enzymes / proteins affect the life cycle of ACh?
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- ChAT = Choline acetyl transferase (synthesizes ACh from Choline and Acetyl-CoA)
- CHT = Choline Transporter (brings Choline into nerve terminal) - VAChT = Vesicular ACh Transporter (pumps synthesized ACh into vesicles for NT release) - AChE = Acetylcholinesterase (degrades ACh at synapse into Choline and Acetate) |
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Which enzyme synthesizes ACh from Choline and Acetyl-CoA?
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ChAT = Choline Acetyl Transferase
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Which protein brings Choline into nerve terminal for the synthesis of ACh?
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CHT = Choline Transporter
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Which protein pumps synthesized ACh into vesicles for NT release at the synapse?
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VAChT = Vesicular ACh Transporter
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Which enzyme degrades ACh to Acetate and Choline at the synapse?
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AChE = Acetylcholinesterase
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What are "Co-transmitters"? Typical co-transmitters?
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- Multiple signaling molecules released from a single neuron (modulate each other's effects)
- Usually amine NT released at the synapse and a peptide released at extra-synaptic sites |
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Where does synthesis of amine neurotransmitters occur? How is it regulated?
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- At nerve terminals / synapse
- Highly regulated: - NE and Dopamine are regulated by end-product inhibition - ACh is regulated by precursor conc. - Some regulated by enzymatic step (catecholamine synthesis (Tyrosine Hydroxylase) regulated by binding of cofactor, BH4) - Some regulated by presynaptic autoreceptors |
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Where does synthesis of neuropeptide neurotransmitters occur? How is it regulated?
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- In cell on ribosome
- Synthesis is not tied to release - Inducible - Large protein precursors |
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How are amine neurotransmitters stored? What kind of pathway is this?
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- In synaptic vesicles (re-used and contain proteins necessary for release at active zone)
- CONSTITUTIVE secretory pathway |
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How are neuropeptide neurotransmitters stored? What kind of pathway is this?
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- In synaptic vesicles (not re-used; fuse with membrane anywhere)
- REGULATED secretory pathway |
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Why is it important to have mechanisms of inactivating neurotransmitters?
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Signaling can continue until the NT is removed
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What are the major mechanisms of NT inactivation? Examples of NT that use each mechanism?
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- Reuptake (e.g., NE, 5-HT, and DA)
- Enzymatic Breakdown (e.g., ACh) - Diffusion Away (e.g., peptides) - Uptake by Astroglia (e.g., glutamate) |
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What is necessary for NT release?
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Increased Ca2+ intracellularly --> Induces the fusion of vesicle and plasma membrane, allowing for release of intravesicular contents
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What are the relative concentrations of Ca2+ intracellularly and extracellularly at rest? Implications?
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- Intracellular: 100 nM
- Extracellular: 2 mM - Large driving force for entry of Ca2+ if resistance is reduced (channels open) |
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How can intracellular Ca2+ concentrations increase?
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Opening of ion channels and release from intracellular storage sites
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How is Ca2+ handled in the presynaptic terminal?
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- Calcium exchanger - Secondary active transport exchange of Na+ (in) for Ca2+ (out)
- Calcium pumps - SERCA pumps into ER and another pumps out into extracellular space - Calcium channels - allow Ca2+ to enter intracellular space from ER and extracellular space |
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How is the plasticity of brain synapses accomplished?
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Changes in synaptic efficiency
- Alterations in presynaptic neuron (transmitter synthesis, axoaxonic synapses) - Alterations in postsynaptic sensitivity (summation, receptor number, efficiency of coupling) |
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How can transmitter synthesis be altered? Implications?
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- Regulation of rate-limiting step (e.g., Tyrosine Hydroxylase)
- Substrate availability (e.g., Tryptophan) - Enzyme induction - Alters presynaptic neuron - mediates synaptic plasticity |
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How can Axoaxonic Synapses affect presynaptic neurons?
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- Presynaptic inhibition
- Regulation of a single synapse |