LECTURE 10 SYNAPSESIII METABOTROPIC RECEPTORS AND SECOND MESSENGERS

LECTURE 10: SYNAPSESIII: METABOTROPIC RECEPTORS AND SECOND MESSENGERS REQUIRED READING: Kandel text, Chapter 13 NT RECEPTOR TYPE: STRUCTURE KINETICS OF CHANNEL MODULATION PRODUCTION OF 2 ND MESSENGER EFFECT OF NT ON CHANNELS LOCATION/TYPE OF AFFECTED CHANNELS NUMBER OF AFFECTED CHANNELS IONOTROPIC RECEPTORS METABOTROPIC RECEPTORS Multi-subunit channels Usually 7 -TM GPCRs 1 - 5 msec 100 msec to days Almost always NO OPEN Post-synaptic ligand-gated channel 1 NT molecule = 1 opened channel YES OPEN or CLOSE Post-synaptic channel, Voltage-gated channels, Resting channels 1 NT molecule = MANY opened channels

SECOND MESSENGER SYSTEMS OF METABOTROPIC NT RECEPTORS

RECEPTOR-ACTIVATED G-PROTEIN CYCLE: Gs and c. AMP

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 residues within a consensus sequence. E. g. PKA ------Arg-Xxx-Ser-Xxx-------O- ------Arg-Xxx-Ser-Xxx------ADP HO-P=O O- ATP

Gbg-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 CURRENT MONITOR Pipet Solution Same as Extracellular Bath 0 CL OS E N OP E Ipipet CL OS E OP E N CHANNEL STATUS

SINGLE CHANNEL RECORDINGS FROM EXCISED INSIDE-OUT PATCH CURRENT MONITOR pipet extracellular solution bath intracellular solution

CELL-ATTACHED PATCH AND INSIDE-OUT PATCH RECORDINGS SHOW SEROTONIN ACTS THROUGH c. AMP 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 Gbg

IONOTROPIC NMDA RECEPTORS GENERATE CALCIUM SECOND MESSENGER: CALCIUM-CALCINEURIN PATHWAY OPPOSES DOPAMINE-c. AMP PATHWAY

METABOTROPIC SECOND MESSENGERS c. AMP and CALCIUM INDUCE SLOW ONSET LONG-LASTING SYNAPTIC MODIFICATIONS THROUGH NEW PROTEIN SYNTHESIS Calcium influx through NMDA receptors into post-synaptic dendrite induces protein synthesis from dendritic m. RNAs, resulting in slow-onset long-lasting post-synaptic modification c. AMP 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 RELEASE READING: Kandel text, Chapters 14, 15