Synaptic Integration: Second Messengers (Ch 9)

2 types of indirect

G-protein coupled and tyrosine kinase

G-protein coupled

• activate guanosine triphosphate (GTP)-binding proteins

• 2nd messengers or directly activate channels

Tyrosine kinase

initiate cascade of protein phosphorylation reactions

What does cAMP do?

activates protein kinase A (PKA)

substrates for PKA

• voltage-gated ion channels

• ligand-gated ion channels

• synaptic vesicle proteins

• enzymes involved in transmitter biosynthesis

• proteins that regulate gene transcription

intra 2nd messengers

confined to where they are produced

trans 2nd messengers

can cross the cell membrane to have effects on other cells

DAG (2nd messenger)

recruits protein kinase C and can phosphorylate lots of other proteins

IP3 (2nd messenger)

activates intracellular Ca2+ stores

what does Ca2+ do

• acts as a 2nd messenger itself and mobilizes other Ca stores

• binds to calmodulin which in turn activates another kinase leading to cellular responses

what do kinases (Ca2+) do?

have important roles in long term memory

Phospholipases (PLA, PLC, PLD) hydrolyze…

endocannabinoids and arachidonic acid

which is the most common G-protein receptor in the brain?

CB1

what binds to CB1 receptors?

endocannabinoids and THC

transcellular messengers

are lipid loving, allowing them to act between cells

where are CB1 receptors located?

axons and presynaptic terminals

what do CB1 receptors do?

inhibit release of neurotransmitters, postsynaptic control of presynaptic receptor

Endocannabinoids are made after ___ changes in the postsynaptic cell, then diffuse to presynaptic cell to bind to CB1 receptors

Ca++

gaseous messengers

• CO and NO

• pass through membrane

• short-lived activity

• activate cGMP

tyrosine kinase ligands

peptide hormones like growth factors or insulin

tyrosine kinase ligands often lead to…

changes in gene transcription

presynaptic modulation mechanism

modulate the activity of K+ and Ca++ channels, and transmitter release machinery

presynaptic modulation effects

regulate the efficacy of transmitter release and thus the size of the fast postsynaptic potential

postsynaptic modulation mechanism

modulate ionotropic receptors

postsynaptic modulation effects

directly alters the amplitude of potentials

2nd messenger modulation in soma

alters a variety of electrical properties

________ turn off second messenger cascades by _______

phosphoprotein phosphatases, removing phosphoryl groups from proteins