LECTURE 10: SYNAPSESIII: METABOTROPIC RECEPTORS AND SECOND MESSENGERS

REQUIRED READING: Kandel text, Chapter 13

IONOTROPIC RECEPTORS METABOTROPIC RECEPTORS

STRUCTURE Multi-subunit channels Usually 7-TM GPCRs

KINETICS OF CHANNELMODULATION

1 - 5 msec 100 msec to days

NT RECEPTOR TYPE:

PRODUCTION OF2ND MESSENGER

Almost always NO YES

EFFECT OF NTON CHANNELS

OPEN OPEN or CLOSE

LOCATION/TYPE OFAFFECTED CHANNELS

Post-synaptic ligand-gatedchannel

Post-synaptic channel,Voltage-gated channels,

Resting channels

NUMBER OFAFFECTED CHANNELS

1 NT molecule =1 opened channel

1 NT molecule =MANY opened channels

SECOND MESSENGER SYSTEMS OF METABOTROPIC NT RECEPTORS

RECEPTOR-ACTIVATED G-PROTEIN CYCLE: Gs and cAMP

PHOSPHATIDYL INOSITOL BIS-PHOSPHATE IS SOURCE OF SEVERAL SECOND MESSENGERS

Gq-ACTIVATED PHOSPHOLIPASE-C GENERATES TWO SECOND MESSENGERS

MANY SECOND MESSENGERS ACTIVATE SERINE/THREONINE PROTEIN KINASES

Each S/T-protein kinase phosphorylates exposed serine or threonine residueswithin a consensus sequence. E.g.

------Arg-Arg-Xxx-Ser-Xxx------- ------Arg-Arg-Xxx-Ser-Xxx-------

HO-P=O

O-

-

O-

ATP ADP

PKA

G-ACTIVATED PHOSPHOLIPASE-A GENERATES ARACHIDONIC ACID:

AA METABOLISM CREATES SECOND MESSENGERS

SEROTONIN CLOSES S-TYPE POTASSIUM CHANNELS IN APLYSIA SENSORY NEURONS

SINGLE CHANNEL RECORDINGS FROM CELL-ATTACHED PATCH

Ipipet0

CLO

SE

OPE

N

CLO

SE

OPE

N

CURRENTMONITOR

CHANNEL STATUS

Pipet SolutionSame as

Extracellular Bath

SINGLE CHANNEL RECORDINGS FROM EXCISED INSIDE-OUT PATCH

CURRENTMONITOR

pipet extracellularsolution

bath intracellularsolution

CELL-ATTACHED PATCH AND INSIDE-OUT PATCH RECORDINGS SHOW SEROTONIN ACTS

THROUGH cAMP SECOND MESSENGER TO CLOSE S-TYPE K+ CHANNELS

CELL-ATTACHED PATCH AND INSIDE-OUT PATCH RECORDINGS SHOW FMRF-AMIDE ACTS

THROUGH AA SECOND MESSENGER TO OPEN S-TYPE K+ CHANNELS

MUSCARINIC ACETYLCHOLINE RECEPTORS CLOSE M-TYPE POTASSIUM CHANNELS:TRANSFORMATION OF EPSP-INDUCED FIRING RESPONSE

ACETYLCHOLINE OPENS GIRK VIA NON-DIFFUSIBLE G

IONOTROPIC NMDA RECEPTORS GENERATE CALCIUM SECOND MESSENGER:CALCIUM-CALCINEURIN PATHWAY OPPOSES DOPAMINE-cAMP PATHWAY

METABOTROPIC SECOND MESSENGERS cAMP and CALCIUM INDUCESLOW ONSET LONG-LASTING SYNAPTIC MODIFICATIONS

THROUGH NEW PROTEIN SYNTHESIS

Calcium influx through NMDA receptors into post-synaptic dendriteinduces protein synthesis from dendritic mRNAs,

resulting in slow-onset long-lasting post-synaptic modification

cAMP production by serotonin receptor-Gs system in presynaptic axon induces specific gene transcription and translation,

resulting in slow-onset long-lasting pre-synaptic modification

NEXT LECTURE: NEUROTRANSMITTERS AND RELEASEREADING: Kandel text, Chapters 14, 15