part 8 Flashcards
the excitatory action of an EPSP is when?
membrane depolarizes closer to threshold of action potential, thus increasing excitability.
Describe Excitatory Postsynaptic Potentials (EPSP).
depolarization caused by an increase in permeability of Na+ and K+ channel
What leads to an Inhibitory Postsynaptic Potential (IPSP)?
hyperpolarization caused by increase in permeability of Cl- or K+ channel
– Influx of Cl- ions and efflux of K+ ions hyperpolarize membrane
describe the Inhibitory action of an IPSP?
membrane hyperpolarizes away from threshold, decreasing excitability.
Excitatory synapses usually occur on?
dendrites
inhibitory synapses usually occur on ?
cell bodies
simultaneous activation of excitatory synaptic potentials from different regions is known as ?
Spatial summation of psp’s
successive synaptic potentials from same synapse can summate to create overall excitation or inhibition. this is known as?
Temporal summation of PSP’s
what produces EEG waves?
Synchronization of PSPs among large populations of neurons
“analog” information processing of PSPs is done at what two regions of a neuron?
Dendrites and cell bodies
Axon potential initiation happens at the ?
Axon Hillock
“digital” information is processed by the ?
Axon
Non-gated channels have ___ ion channels and are located __?
K+
along whole cell except initial segment & nodes of Ranvier
Voltage gated channels have __, __, __ ion channels and are located __?
Na+, K+, Ca++
(Na+, K+) Initial segment, nodes of Ranvier (APs),
(Ca++) Axon terminal (transmitter release)
neruotransmitter/ ligand gated channels have __, __, __ ion channels and are located __?
Na+,K+, Cl-
(Na+,K+) Postsynaptic dendrite membranes (EPSP’s)
(Cl-) Postsynaptic cell body membrane (IPSP’s)
what does METABOTROPIC (INDIRECTLY) GATED TRANSMISSION involve?
Involves cell signaling systems that utilize enzymes and/or genomic regulation (“metabolism”)
Compare metabotropic and Ionotropic transmissions
ionotropic transmission: the receptor for the transmitter is on the ion channel itself. The response is fast, but of short duration
metabotropic transmission: the receptor is a membrane protein that activates a cascade of enzymes that stimulate synthesis of second messengers and/or alter gene activity.
These proteins are a complex of α, β, and γ units that dissociate from the receptor protein and activate other enzymes to produce second messengers.
G proteins
They utilize GTP (Guanosine triphosphate), hence the name G.
these Proteins are the most important signal transducing molecules in cells
G PROTEINS
two ways in which Ligand receptor activates G protein?
- Transmitter causes receptor to bind with inactive G protein
- GTP replaces GDP, activating the G protein
3 ways in which α, β, γ portions of activated G protein generate cell activity?
- Direct action on the permeability of ion channels
- Activation of second messengers (eg. cAMP)
- Gene transcription of proteins
Explain how Direct action of G proteins on ion channels works?
• β, γ portions G protein bind directly onto ion channels to alter its permeability
for example.. In heart deceleration, vagus nerve stimulates the SA node using Ach to open K channels and hyperpolarize the cell. This inhibits cardiac action potentials and decreases the heart rate
two primary examples of second messengers that occur in all body cells?
cAMP and IP3/DAG
explain the second messenger cascade?
G protein >Enzyme > 2nd messenger >Effector (kinase or other enzymes) >Cell function
explain the entire metabotropic action leading to a cell response
Ligand (first messenger) binds to a receptor, this activates a G protein, this activates an amplifier enzyme (adenylate C, guanylate C or phospholipase C) these get phosphorlated to ATP, GTP or PIP, which activate second messangers (cAMP,cGMP, IP3/DAG) which activate a intracellular effector which leads to a cell response!!
explain the funamentals of cyclic AMP
- G protein stimulates adenyl cyclase to convert ATP to cAMP
* cAMP activates the enzyme PKA via phosphorylation.
explain step 1 of the signal transduction pathway using cAMP
a signaling molecule activates GPCR (G protein coupled receptor). this causes G protein to bind GTP, thereby promoting the dissociation of the α subunit from the β/γ dimmer.
explain step 2 of the signal transduction pathway using cAMP.
the binding of the α subunit to adenyl cyclase promotes the synthesis of cAMP from ATP.
explain step 3 of the signal transduction pathway using cAMP.
cAMP binds to the regulatory subunits of PKA, which releases catalytic subunits of PKA.
explain step 4 of the signal transduction pathway using cAMP.
the catalytic subunits of PKA use ATP to phosphorylate specific cellular proteins thereby cause a cellular response.
Stimulatory vs inhibitory effects of G proteins on cAMP depends on this portion of a G protein?
alpha portion
total amount of cAMP in cell depends on balance between the two effects.
Explain the basic differences in signal amplification between metabotropic and ionotropic transmission
- Metabotropic transmission uses G proteins to amplify a cell’s response to ligands / transmitters.
- Ionotropic transmission is fast with a short duration
explain Some actions of cAMP
• cAMP induces PKA phosphorylation of contractile proteins, ion channels, enzymes and regulatory proteins.
• Produce long term (hours) changes in neuronal excitability by altering permeability of “non- gated” K+ channels.
• cAMP regulates metabolic pathways
– Convert glycogen to glucose in liver & muscle cells
– Release fatty acids from adipose cells
In adipocytes, cAMP stimulates hormone sensitive lipase (HSL) to facilitate triglyceride breakdown into fatty acids.
how are second messengers inositol triphosphate (IP3) and
diacylglycerol (DAG) created from G proteins?
G protein activates phospholipase C (PLC), which cleaves phosphatidyl inositol (PIP) into second messengers (IP3 and DAG)
IP3 releases Ca++ from endoplasmic reticulum. what becomes of these two molecules?
– Ca regulates smooth muscle contraction, cell secretion, etc.
– IP3 is degraded to inositol and reincorporated into the membrane. (Inhibited by Lithium)
DAG (Diacylglycerol) activates the enzyme protein kinase C, which promotes ?
cell division and proliferation
Li acts in these two areas to improve memory?
hippocampus in the limbic system
Lithium has many actions including:
mood and memory stabilization by:
• Inhibition of glycogen synthase kinase-3 (GSK-3) blocks protein degradation and apoptosis of neurons
• Inhibition of inositol monophosphatase (IMP-ase) leads to increased IP3 and long term modulation of synaptic connections and modulation of neuronal circuits
G proteins can alter genomic regulation through the use of cAMP by this mechanisim?
cAMP > PKA > CREB
– PKA phosphorylates a transcriptional activator CREB (cAMP
response element binding protein).
CREB proteins are transcription factors that can produce long term changes in the functions of ion channels.
briefly explain up or down regulation in ion channels
cAMP-activated proteins interact with regulatory TF on the DNA to up or down regulate gene expression
• Effects last for hours to several days
• Mediated by changes in rate of receptor turnover, receptor gene transcription or receptor mRNA turnover.
