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Chemical Synapse

Synapse that uses neurotransmitters as a messenger to talk to each other and pass a signal

1

Electric Synapse

Uses ionic currents as the main method of communication with other cells. Here the synapses are mechanically connected via a gap junction, so current can be exchanged.

2

Metabotropic Receptor

Couples with G-proteins

3

Ionotropic receptor

functions as a ligand-gated (activated) ion channel

4

Presynaptic heteroreceptor

located on presynaptic terminals

5

Presynaptic autoreceptor

located on presynaptic terminals, serves as a negative feedback mechanism to regulate firing and neurotransmitter release

6

Postsynaptic receptors

Located on postsynaptic target cells

7

Excitatory postsynaptic current (EPSC)

positively charged ions flow into a postsynaptic cell during membrane depolarization

8

Excitatory postsynaptic potential (EPSP)

membrane potential (Vm) depolarization in postsynaptic cell (in response to excitatory impulses)

9

Inhibitory postsynaptic current (IPSC)

Negatively charged ions flow into a postsynaptic cell during membrane hyperpolarization

10

Inhibitory postsynaptic potential (IPSP)

Vm hyperpolarization in postsynaptic cell (in response to excitatory impulses)

11

Acetylcholine (ACh)

Memory, sensory processing, motor coordination, neuromuscular junction, ANS and PANS function

12

Norepinephrine (NE)

CNS sensory processing, cerebellar function, sleep, mood, learning, memory, anxiety, and SANS

13

Dopamine (DA)

Motor regulation, mood, addiction, reinforcement, olfaction, hormone control concentration, and hypoxic drive

14

Serotonin (5-HT)

Emotional processing, mood, appetite, sleep, pain processing, hallucinations, and reflex regulations

15

Histamine (H)

Sleep, sedation, and temp regulation

16

Gamma amino butyric acid (GABA)

Major inhibitory neurotransmitter in the CNS

17

Glutamate (Glu)

Long-term potentiation, memory, major excitatory fxn in the CNS and PNS

18

Glycine (Gly)

Major inhibitory fxn in the CNS

19

Monamine Pathways in CNS

Norepinephrine (NE) - Locus Coeruleus--> cerebral cortex, limbic sys, cerebellum, and spinal cord
Serotonin (5-HT) - Raphe nuclei (RN)--> whole brain and spinal cord
Dopamine (DA) - Ventral tegmental area and Substantia nigra pars compacta (SNPC)--> basal ganglia, limbic system, and prefrontal cortex
Acetylcholine (ACh)--> Septal nuclei, nucleus basalis--->brain regions

20

G-Proteins/Second messengers

Bind GDP and GTP, coupled with metabotropic receptors (GPCRs), activate or inhibit activity of effectors,

21

Gs

Stimulatory, Active during high levels of cAMP

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Gi

Inhibitory, Active during low levels of cAMP

23

Gq

Hydrolyzes, Second messenger is IP3 and DAG

24

Go

Second Messenger is Arachidonic Acid

25

Gap junction

A type of synapse that mechanically connects the cytoplasm of two cells allowing for the conductance of electrical signal as the messenger. Can be conducted bi-directionally and are smaller in the postsynaptic cell than in the presynaptic originating cell
Formed by connexon, made up of 6 connexin units - 4 membrane spanning regions, and the opening is smaller than a chemical synapse 3.5 nm v.s 20-40 nm

26

Resting Membrane Potential (RMP)

cell is at equilibrium and the net current (I) = 0
RMP depends on equilibrium potential (Ek) of K+, membrane at rest is primarily permiable to potassium

27

Ohm's Law

The strength of a direct current (I) is directly proportional to the potential (voltage) different (^E, ^V and inversely proportional to the resistance (R) or reciprocal of the conductance R= 1/C) of the circuit.
V = IR
or
I = V/R

28

Nernst Equation

Relates the concentration gradient to the electric (potential) gradient that balances it. Determine equilibrium potential of a cell.
Es = E1 - E2 = RT/zsF(ln)[S]2/[S]1
S: arbitrary ion
S2 and S1: external and internal concentration of ion
E1-E2: membrane potential difference
R: universal gas constant
T: absolute temperature (kelvin) 273.15 + degrees in C
z: valence of the arbitrary ion (elementary change Na+=1 Ca2+=2 etc)
F: the Faraday constant
ln: natural log

29

Voltage Gated Ion Channels

Na, K, Ca
alpha1 subunit: "pore-forming" protein that has 4 homologous transmembrane domains (TM), each TM is a helix with 6 transmembrane spannings
Selective filter SS1-SS2 connects S5 and S6 to form pore
S4 segment fxns as a voltage gated sensor

30

Ligand gated Ion channels (Ionotropic receptors)

clustered in the postsynaptic membrane and open rapidly after binding with selective agonists.
Activation of ligand-gated ion channels induced Vm change
Ex: Nicotinic ACh receptor, Glutamatergic N-methyl-D-aspartate receptor (NMDAR), y-aminobutyric acid A-receptor (GABAaR)

31

Nicotinic Acetylcholine (ACh) Receptor (nAChR)

17 subunits, belongs to the superfamily pentametric ligand gated receptors (GABAaR, GlyR, 5-HT3R)
Positive ion channel, Na and others, but does not allow passage of anions. Depolarizes Vm and causes muscle contraction or neuron firing.
Agonists: ACh, nicotine, choline, cabachol, etc
Antagonists: alpha-bungarotoxin (venom) and tubocuraine (arrow poison) = irreversible binding of ACh receptors causing paralysis, respiratory failure, and death.
Prolonged or repeated exposure to ACh reduces nAChR conductance, sensitivity recovers only when ACh is removed.
Used in motor neurons for transmission of AP signal to muscles at the neuromuscular junction, also in the release of dopamine in the brain from nicotine stimulus.

32

Glutamatergic NMDA Receptor (NMDAR)

ligand gated, ionotropic receptor; belongs to the glutamate receptor family.
Non-specific cation channel (highly conductive for Ca2+) found only in CNS of vertebrates.
Tetramer of homologous subunits, at least 7 genes
Agonist and co-agonist: Requires simultaneous binding of glutamate (agonist) and glycine (co-agonist). Interacting with AMPA receptor
Antagonist: selectively blocked by AP5 and memantine
Mediates excitatory synaptic activity, acts as a coincidence detector for presynaptic glutamate release and postsynaptic Vm depolarization
Critical in synaptic plasticity; can induce excitotoxicity.
Phosphorylation increases its activity and Ca influx

33

GABAa Receptor

Are ion channels
Belong to the superfamily of pentameric ligand-gated ionotropic receptors. Has 5 subunits, each with 4 helical membrane spannings
15 different subunits in 7 families, combinations may alter function in regulating Cl opening (hyperpolarization of Vm)
Agonist: GABA
Function: a binding substrate for the major inhibitory neurotransmitter GABA in the CNS. Regulates inhibitory neuronal responses by conducting Cl influx via activating GABAaR/Cl channels = Vm hyperpolarization.
Mutation of GABAaR is related to Huntington's disease, Epilepsy, and alcoholism