HL PDA III Exam I - Principles of Neuropharmacology LOs

What are the 3 structural elements of a neuron?

dendrites, cell body (soma), and axon

What is a dendrite?

the part of the neuron that receives input/information from other neurons

What is a cell body?

the part of the neuron that is also called the soma

What is an axon?

the part of the neuron where NT is released (electrical → chemical signals)

True or False: axo-dendritic are the most common axons

True

Explanation: terminal buttons of an axon can form synapses with dendrites and these are known as axo-dendritic

What is an axon hillock?

the part of the neuron where we transition from soma to axon

True or False: if the summation of local potentials at the axon hillock reach -70mV, an action potential is generated

False

Explanation: it is at -50mV! also an AP is defined as a rapid change in membrane potential that's propagated down the axon

What happens when the membrane potential reaches -50mV?

Depolarization

Explanation: large numbers of voltage-gated Na+ FAST channels open causing the membrane potential to rise by Na influx to reach +40mV which is considered the rising phase of the AP

What is the definition of depolarization in regards to Na+?

influx of Na+ that causes the membrane potential to be more positive

What happens when the membrane potential reaches +40mV?

Absolute Refractory Period

Explanation: the Na+ channels close and CANNOT open, it is impossible to stimulate further/again

True or False: during the absolute refractory period, voltage-gated K+ channels open for influx

False

Explanation: when these channels are open, K+ efflux occurs which leads the membrane potential to become more negative (-70mV)

What happens when the membrane potential reaches -70mV?

Relative Refractory Period: can stimulate again with a large enough stimulus

Hyperpolarization: K+ efflux causing more negative membrane potential

True or False: after the membrane potential reaches -70mV, all voltage-gated channels close and the neuron returns to resting membrane potential

True

True or False: if an AP has propagated down the neuron and arrives at the axon terminal, voltage-gated Ca2+ channels open during chemical transmission

True

Explanation: this leads to Ca2+ influx and a more positive membrane potential

What happens in chemical transmission after voltage-gated Ca2+ open?

Ca2+ interacts with proteins on the membrane of synaptic vesicles to stick to the presynaptic cleft causing release of NTs

True or False: Ca2+ interacting with proteins on the membrane of synaptic vesicles to stick to the presynaptic cleft causing release of NTs is known as a "Ca2+ dependent process"

True

What is exocytosis during chemical transmission?

release of NTs

True or False: NTs may diffuse across the synapse and bind to ionotropic receptors which opens the ion channel causing a change in the membrane potential within the presynaptic neuron

False

Explanation: everything is true except it's within the POSTsynaptic neuron

What is depolarization within chemical transmission?

positive change in membrane potential to reach threshold and the postsynaptic neuron will fire an AP

True or False: chemical transmission within a neuron is linked to electrical transmission between neurons

False

Explanation: chemical transmission is BETWEEN neurons and electrical transmission is WITHIN a neuron

What happens after depolarization during chemical transmission?

NTs go crazy lol

True or False: NTs may diffuse across the synapse and bind to G-protein coupled receptors (GPCRs)

True

Explanation: GPCRs produce biochemical changes in the postsynaptic neuron

True or False: NTs can also bind to presynaptic inhibitory autoreceptor, undergoreuptake, can be broken down by an enzyme, AND/OR be moved by transporters on glial cells

True

Explanation: "Reuptake" is when NTs are grabbed by an NT transporter → back into the presynaptic neuron. Transporters on glial cells → glia is ONLY glutamate and GABA

What are the 2 types of extracellular receptors?

ionotropic and metabotropic

What are ionotropic receptors?

Ion channel receptors

Example: ligand-gated ion channels

What are metabotropic receptors?

Biochemically coupled to effectors/second messengers & have enzymatic activity

Example: G-protein coupled receptors

True or False: G-proteins are heterotrimers with alpha, beta, and gamma subunits

True

True or False: the alpha subunit of a G-protein is bound to GDP

True

True or False: during GCPR signaling, an agonist ligand binds to the extracellular domain of GCPR

True

What is an example of an agonist ligand?

NT or a drug

What happens once an agonist ligand binds to extracellular domain of GCPR?

Conformational change in the receptor which leads to conformational change of the G-protein → GDP pops off of the alpha subunit to bind to GTP

True or False: there is lots of GDP floating around

False

Explanation: there is GTP floating around

What happens with the alpha subunit after it binds to GDP?

Conformational change causes the alpha to separate from beta-gamma

Explanation: alpha and beta-gamma can interact with effector molecules (enzymes that have 2nd messenger inside the cell)

What happens with the 2nd messenger in GPCR signaling?

Causes biochemical changes inside the cell

True or False: alpha subunit is NOT an enzyme that catalyzes hydrolysis of GTP → GDP

False

Explanation: it is an enzyme that does this! Also, alpha changes back to OG conformation that prefers binding to beta-gamma and its receptor

What is the function of Gs within the alpha subunit?

interacts with effector enzyme adenylyl cyclase which converts ATP → cAMP → activate PKA → phosphorylation cascade

What is the function of Gq within the alpha subunit?

interacts with effector molecule alpha Q (that's NOT adenylyl cyclase) → activates PLC → breaks PIP2 into DAG + IP3

→ IP3 releases Ca2+ from ER

→ DAG + Ca2+ activate PKC

True or False: PKC is similar to PKA

True

Explanation: they are kinase enzymes

What is the function of Gi within the beta subunit?

interacts with its effector molecule K+ channel → subunit binds → opens the channels → K+ efflux → hyperpolarization of the neuron

What are the G-protein alpha subunit subtypes?

Gs, Gi, Gq

What is the effector molecule of Gs within alpha subunit?

adenylyl cyclase (stim)

What is the effector molecule of Gi within alpha subunit?

adenylyl cyclase (inhib)

What is the effector molecule of Gq within alpha subunit?

phospholipase C (stim)

What is the 2nd messenger of Gs within alpha subunit?

cAMP (increased)

What is the 2nd messenger of Gi within alpha subunit?

cAMP (decreased)

What are the 2nd messengers of Gq within alpha subunit?

Diacylglycerol (DAG) and Inositol Trisphosphoate (IP3)

What is the altered activity of Gs within alpha subunit?

increased PKA activity from increased cAMP

What is the altered activity of Gi within alpha subunit?

decreased PKA activity from decreased PKA activity

What is the altered activity of Gq within alpha subunit?

increased PKC activity from DAG and Ca2+ release from the ER because of IP3

What is the G-protein beta-gamma subunit subtype?

Gi

What is the effector molecule of Gi within the beta-gamma subunit?

K+ channel AND voltage-sensitive Ca2+ channel

What is the altered activity of Gi within the beta-gamma subunit?

Hyperpolarization from K+ channel AND inhibits NT release from voltage sensitive Ca2+ channels

What sites and steps of neuronal activity can a drug act on to produce an effect?

Agonist molecules (i.e., drugs or NT) can alter the membrane potential by acting directly on ion channels or through G-protein coupled mechanism

What is the blood brain barrier (BBB)?

exists because of differences in morphology of endothelial cells of brain capillaries vs typical capillaries

True or False: brain capillaries have no intracellular clefts

True

Explanation: this is because adjoining endothelial cells are fused together at tight junctions

True or False: brain capillaries have fenestrations and pinocytic vesicles

False

Explanation: they have neither

What is the purpose/function of glial cells in brain capillaries?

tightly surround the capillaries to form another barrier

Is the BBB an absolute barrier?

No

True or False: BBB blocks water-soluble and ionized compounds

True

Explanation: BBB prefers lipophilic compounds BUT there are exceptions

What do specialized transporter molecules do within the BBB?

bring amino acids, glucose, and other nutrients in

What do efflux pumps do within the BBB?

pump lipophilic molecules out

True or False: the BBB has receptor mediated transcytosis

True

True or False: pericytes do not contribute to the BBB

False

What molecules typically can cross the BBB?

small, lipid-soluble (lipophilic) molecules, like gases (oxygen, carbon dioxide), certain hormones, and small non-polar molecules