Modulation of Synaptic Transmission:

1
???? 13?Principles of Neural Science
4th-edition Chapter 13

• ???????????????
• Modulation of Synaptic Transmission
• Second Messengers

? ?? sshi_at_brn.dis.titech.ac.jp
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Figure 13-1

• ???????????????receptor?receptor?effector????????
  ?????????????????
• A. Direct gating(Ionotropic receptor)
• ????????receptor?effector????receptor?????????????
  ????receptor?????????????
• B. Receprots that indirectly gate ion channes
  fall int tyow families.
• Metabotropic G protein-coupled receptors
• second-messenger cascade??????GTP????????????????
  ??????????????????????
• 2. Receptor tyrosine kinases
• ????????????????????????????????????????????????e
  ffector??????

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Figure 13-2
Adenylyl cyclase
Gs
Gq
4
Figure 13-3
???G-protein?????(GTP????????????)?7?????????????
(Figure 13-3??) ß2-?????????????????G-protein???
???????????????(ß1-????????????????ACh????????????
???) ?????????????????????????????2?????????????
????(Asp113) ?????(SerSerine reside)????????????
??????????
5
Figure 13-4
??????? 1.???????????????????? 2.????????????????
?????????Gs?????????????? 3.??2???????Gs?????????
?????GDP?GTP??????????? 4.GDP?GTP??????a-subunit?
Gs??????????a-subunit???????????????????? 5.
a-subunit??????????????????????cAMP???(????????)
6. a-subunit????????????GTP?????????????ß?????????
??G-protein???? 7.???????????????????????????????
?????????
as
?????????
??subunit
a-subunit
to Figure 13-12
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Figure 13-5
?????????(adenylyl cyclase)?ATP?cAMP?????????????
?????(phosphodiesterase)?cAMP?AMP????
cAMP-dependent protein kinase? ????(catalytic
subunit)? ????(regulatory subunit)???? cAMP???????
?????????????????????????????ATP???????????
????????????????????(phospatase??????)???????????
????????????????????????????
Pi
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Figure 13-6
RRegulatory subunit CCatalytic subunit
???protein kinase?????????????????
A?????R?C????????????????????
B-D???????????????????R?C?????????????????????????
???????????????????????????????????
E??????????????R?????C?????????????????????????2??
????????(R????)???????????????????????????????????
?????????????
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Figure 13-7
GTPGuanosine Tri Phosphate
?????3??? PLPhospholipase ????????? PLA2
?????????A2 PLC ?????????C DAGDiacyl
glycerol ?????????? IP3Inositol
trisphosphate ??????3??? Endoplasmic
reticulum??? ?????????????3?????????????????????
?????? ??????????????????????????????????????????
???????PIP2????Reseptor?Transmitter??????G-Protein
???????PKC???????? ??????????PIP2?IP3?DAG???????
IP3???????????IP3????????????????Ca2???????
Protein Kinase C?Ca2/calmodulin(???????)??Protein
Kinase?????Ca2??????Substrate
protein(??????)?ATP??????????????
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Figure 13-8
4-Bromophenacyl bromide ???????
NDGANordihydroguaiaretic acid ????????????
Arachidonic acid ?????? Lipoxygenase ????????
?? Cycloosygenase ?????? Indomethacin???????
??????????? lipase?????? ???????????????????
???????PLA2???????????????????????????????????????
???
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PIP2
????? IP3???
??????
??????
????? ???????
????? DAG????
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Figure13-9
??????????????????????????????????????????????
?????????????G-protein???????????????????????????(
membrane-permeable modulator)(???NO??)????????????
membrane-permeable modulator????????????????????
?????????????????????????????????
???????(long-term potentiation)???????????????????
?????????(????????????????????????????????(??))

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Figure13-10
A.??????????K?Ca2???????????????????????????????
??????? B.???????????????????????????????????????
??????????????
C.????????????resting?voltage-gated???????????????
?????????????????????????
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Figure 13-11
????????????(ganglion)??????????????????????????
A. post??????Ach???????????Ach????????????EPSP???
????????????Ach???????G protein????????EPSP??????
M-type??????????M-type K?????????????K????????
?????????????????????????????????????M-type
K??????????????????
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Figure 13-11
B.????(voltage clamp)???? voltage
clamp????????????????Ik??????????
?????Vr???????Vt???1??????????????Control?????????
????????????????????????????M-type K
channel?????????????K??????????M-type K
channel??????????????????????K????????? C.??????
?M-type???????????????????????????????????????
??EPSP????M-type???????????????????????????slowEPS
P??????????????M-type K????????????????(???accomm
odation???)?slowEPSP???????????????K?????????????
????????(???anti-accommodation???)????????????
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Figure 13-12
?????????????????????????????????slow synaptic
action?S-type K??????????? A.???????????????????
??????????????????????????????????????????????????
????????????????????????
C.?????????????S-typeK???????????????????????????
???????(??????)??? ????Vm?????Im?????????????????
?????????????????????????????????????????????Ohm??
?????????????????(?V?Im/gi)??????????????????????
??????
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Figure 13-12
????? ??????????
5-HT????? (5-hidroxytryptamine) S-type
receptor Resting K serotonin- sensitive
channel B.???????????????????????(5-HT-R)????????
???Figure13-4????cAMP?????PKA????cAMP?ATP????S-typ
e??????????
??? ??????
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Figure 13-13
Patch-clamp?????S-type K???????
A.?????(5-HT)??????5????3????????????????????????
???????????????????????S-type K????????????????A2
?????????????S??????????????
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Figure 13-13
B.??????????cAMP?????????????3??S???????3?????????
C.cAMP?ATP??????????PKA(cAMP???protein
kinase)???????????(cell-free)S-type???????????????
??4????2??????????????????????ATP????????????PKA??
????
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Figure13-14
??????????????????S-type K?????FMRFamide??????
A.???????????????????????????FMRFamide????????????
????S-type K???????????12-HPETE?????????????????F
igure13-8?? B.FMRFamide??????????????????????????
??????????????????????????????????????? C. S-type
K?????FMRFamide??????Patch-clamp?????? 1.FMRFamid
e????S-type???????????????? 2.12-HPETE????????????
??(cell-free)?????S-type???????????(????????)
FMRFamide?12-HPETE????????????????????????????
FMRFamide Phe-Met-Arg-Phe-amide
VmIm/gi
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Figure13-15
G protein??????????????????????????????????????
GIRKG protein-regulated
Inward-rectifying K channel Vagal nerve
stimulation?????? A. GIRK???????ACh?????????????
???Gi protein???????????????????????(Adenylyl
cyclase??)????????????????????????subunit?????????
?????????? B.?????????????????????????????GIRK???
??????????????????????????????????? C.
????????????????3??GIRK??????????????
??????????????????????ACh????????????????
????????????????ACh????K????????GIRK????K???????
????????????????????
???????K????????????????
K????????
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Figure13-16
??????????????cAMP???????Ach????????????
ACh?????????????????(desensitization)??????(??????
??????????????????????????????????????????????????
????????????)ACh???????????PKC???????????????????
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Figure13-16
?????????????protein kinase?????????
?????????????protein kinase???????????????????????
??????????????????????????????????cAMP??protein
kinase(PKA)???inhibitor-1?????????????phosphatase-
1??????????
inhibitor-1????????????????(calcineurin),Ca2,????
???(calmodulin) ?????????????????????????NMDA-type
????????????????????????????
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Figure13-18
Enhancer?????? Promoter(DNA??)??????
?????????????????????????????????
???????????????????????cAMP???????????????(PKA????
???)?????????????kinase?K????????????(???????????
???K????) ?????????????????????PKA???????????????
????????????????????????? ???????????????????????
???????????????????????
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Overall View
????????????????????????????????3????????????????
??????????????????????????????????????????????????
??????????????????????????????????????????????????
??????????????????????????????????????????????????
???????????????????????????????????????????? G
protein???????????????????????????????????????????
???????cAMP??????????IP3?DAG????????????????
??????????????????????????????????????????????????
????????????????????????????????????
??????????????????????????????????????????
??????????????????????????????????????????????????
????????????????????????????????????????????????
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Fin

• Chapter 13
• By Shigemi Sawa
• sshi_at_brn.dis.titech.ac.jp