- Email: [email protected]
Reduction of voltage-dependent Mg2+ block of NMDA receptor response by neuronal injury
S64
018
Mg,2+ BLOCK OF NMDA RECEPTOR RESPONSE
REDUCTION OF VOLTAGE-DEPENDENT BY NEURONAL INJURY
JUNICHI
NABEKURA.
Dept. of Physiology,
YOSHIHIKO
YURUKAWA
AND NOR10 AKAIKE
Fat. of Medicine, Kyushu Univ. Fukuoka 812-8582
neuronal injury wcrc The alteration of the voltage dependent Mg 2+ block of NMDA response by in viva investigated on the motoneurons of the dorsal motor nucleus (DMV) acutely dissociated from rats using a nystatin perforated patch recording. Axonal crush of DMV neurons were performed at the vagal nerve bundle at the neck. Reduction of Mg2+ block of NMDA response became obvious at18 hours after axonal injury and lasted until 10 days after the operation. Colchicine did not mimic the axonal injury, suggesting that reduction of Mg2+ block was brought by neuronal injury, not by the blockade of axonal transport. The modulators for intracellular protein kinasc C failed to recover Mg2+ block affected. In addition, a decrease of ifenprodil-sensitive components of NMDAinduced currents after axonal injury suggests that an alternation of subunits composing NMDA rcccptor might hc responsible for the reduction of Mg 2+ block of NMDA response by neuronal injury.
PSD-95 INHIBITS
019
RECEPTOR
PROTEIN KINASE C-MEDIATED POTENTIATION
KENJI SOBUE’ AND MAKOTO INUI’
‘Dept. of Pharmacol., Yamaguchi Univ. Sch. of Med., Ube, Neuropharmacol., Osaka Univ. Sch. of Med., Suita, Osaka 5650871
channels,
potentiation
of the channels,
conditions,
cRNA into Xenopus
to ifenprodil.
NMDA receptor expressed
El/<1
indicating
oocytes.
It has been shown
in oocytes.
‘Dept.
heteromeric
E2/<1
of Neurochem.
that PSD-95
functionally
and
interacting with the COOH NMDA receptor
PSD-95 did not change the basic properties
that protein kinase C markedly
Co-expression
the protein kinase C activities were not significantly
results suggest that
75.5-8505,
The effects of PSD-95 on the channel activity of ~2151 heteromeric
by injection of PSD95
including the sensitivity
activity of
Yamaguchi
protein PSD-95 has been shown to induce clustering of NMDA receptors,
terminal of E subunits of the receptors. were examined
OF NMDA
CHANNELS
YASUE YAMADA’, YASUYO CHOCHI’,
A channel-associated
OF &2&l SUBTYPE
potentiates
of the
the channel
of PSD-95 inhibited the protein kinase C-mediated
modulated
the NMDA receptor channels.
Under
different between oocytes with and without PSD-95.
these These
NMDA receptor channels in viva are less sensitive to protein kinase C by interacting
with PSD-95. L-TYPE
020
PYRAMIDAL
MITSUO TANABE’, ‘Neurosci.
CA’+-CHANNELS
MEDIATE
THE SLOW CA’+-DEPENDENT
K’ CURRENT
IN RAT CA3
CELLS IN VITRO.
BEAT H. GAHWILER’ and URS GERBER’
Res. Labs, Sankyo CO., Ltd., Shinagawa-ku,
Tokyo 140-8710, ‘Brain Research
Institute,
University
of Zurich,
CH-8029 Zurich, Switzerland Single-electrode
voltage-clamp
recordings
contrast, antagonist,
neither
The slow IAHPwas suppressed
w-conotoxin
respectively,
PM), a Ca”-ATPase
MVIIA
attenuated inhibitor
(1 FM) nor o-agatoxin
which depletes
intracellular
Ca2+ stores.
current. which was, however. blocked by isradipine. is necessary
by the selective
this slow outward current.
induced Ca” release from intracellular
Ca” channels
from CA3 pyramidal
The slow IAHPwas significantly
Ca”
Thus. in hippocampal
thapsigargin
and P/Q-type
slice
(K.MeSO,(2 PM).
Ca”
In
channel
reduced by thapsigargin
(10
blocks Ca"-
did not modify high threshold
CA3 pyramidal
intracellular
isradipine
(IO-100 FM) which
stores or by ryanodine
At this concentration
organotypic
voltage jumps
L-type Ca” channel antagonist
IVA (200 nM). an N-type
to trigger the slow IAu~. Furthermore,
signal to induce the slow IAHP.
cells in rat hippocampal
K’ current (slow I*nP) was elicited with brief depolarizing
cultures and the slow Ca”-dependent filled microeletrodes).
were obtained
Ca”
cells Ca” influx through L-type
Ca” stores serve to amplify the initial Ca”
018
Mg,2+ BLOCK OF NMDA RECEPTOR RESPONSE
REDUCTION OF VOLTAGE-DEPENDENT BY NEURONAL INJURY
JUNICHI
NABEKURA.
Dept. of Physiology,
YOSHIHIKO
YURUKAWA
AND NOR10 AKAIKE
Fat. of Medicine, Kyushu Univ. Fukuoka 812-8582
neuronal injury wcrc The alteration of the voltage dependent Mg 2+ block of NMDA response by in viva investigated on the motoneurons of the dorsal motor nucleus (DMV) acutely dissociated from rats using a nystatin perforated patch recording. Axonal crush of DMV neurons were performed at the vagal nerve bundle at the neck. Reduction of Mg2+ block of NMDA response became obvious at18 hours after axonal injury and lasted until 10 days after the operation. Colchicine did not mimic the axonal injury, suggesting that reduction of Mg2+ block was brought by neuronal injury, not by the blockade of axonal transport. The modulators for intracellular protein kinasc C failed to recover Mg2+ block affected. In addition, a decrease of ifenprodil-sensitive components of NMDAinduced currents after axonal injury suggests that an alternation of subunits composing NMDA rcccptor might hc responsible for the reduction of Mg 2+ block of NMDA response by neuronal injury.
PSD-95 INHIBITS
019
RECEPTOR
PROTEIN KINASE C-MEDIATED POTENTIATION
KENJI SOBUE’ AND MAKOTO INUI’
‘Dept. of Pharmacol., Yamaguchi Univ. Sch. of Med., Ube, Neuropharmacol., Osaka Univ. Sch. of Med., Suita, Osaka 5650871
channels,
potentiation
of the channels,
conditions,
cRNA into Xenopus
to ifenprodil.
NMDA receptor expressed
El/<1
indicating
oocytes.
It has been shown
in oocytes.
‘Dept.
heteromeric
E2/<1
of Neurochem.
that PSD-95
functionally
and
interacting with the COOH NMDA receptor
PSD-95 did not change the basic properties
that protein kinase C markedly
Co-expression
the protein kinase C activities were not significantly
results suggest that
75.5-8505,
The effects of PSD-95 on the channel activity of ~2151 heteromeric
by injection of PSD95
including the sensitivity
activity of
Yamaguchi
protein PSD-95 has been shown to induce clustering of NMDA receptors,
terminal of E subunits of the receptors. were examined
OF NMDA
CHANNELS
YASUE YAMADA’, YASUYO CHOCHI’,
A channel-associated
OF &2&l SUBTYPE
potentiates
of the
the channel
of PSD-95 inhibited the protein kinase C-mediated
modulated
the NMDA receptor channels.
Under
different between oocytes with and without PSD-95.
these These
NMDA receptor channels in viva are less sensitive to protein kinase C by interacting
with PSD-95. L-TYPE
020
PYRAMIDAL
MITSUO TANABE’, ‘Neurosci.
CA’+-CHANNELS
MEDIATE
THE SLOW CA’+-DEPENDENT
K’ CURRENT
IN RAT CA3
CELLS IN VITRO.
BEAT H. GAHWILER’ and URS GERBER’
Res. Labs, Sankyo CO., Ltd., Shinagawa-ku,
Tokyo 140-8710, ‘Brain Research
Institute,
University
of Zurich,
CH-8029 Zurich, Switzerland Single-electrode
voltage-clamp
recordings
contrast, antagonist,
neither
The slow IAHPwas suppressed
w-conotoxin
respectively,
PM), a Ca”-ATPase
MVIIA
attenuated inhibitor
(1 FM) nor o-agatoxin
which depletes
intracellular
Ca2+ stores.
current. which was, however. blocked by isradipine. is necessary
by the selective
this slow outward current.
induced Ca” release from intracellular
Ca” channels
from CA3 pyramidal
The slow IAHPwas significantly
Ca”
Thus. in hippocampal
thapsigargin
and P/Q-type
slice
(K.MeSO,(2 PM).
Ca”
In
channel
reduced by thapsigargin
(10
blocks Ca"-
did not modify high threshold
CA3 pyramidal
intracellular
isradipine
(IO-100 FM) which
stores or by ryanodine
At this concentration
organotypic
voltage jumps
L-type Ca” channel antagonist
IVA (200 nM). an N-type
to trigger the slow IAu~. Furthermore,
signal to induce the slow IAHP.
cells in rat hippocampal
K’ current (slow I*nP) was elicited with brief depolarizing
cultures and the slow Ca”-dependent filled microeletrodes).
were obtained
Ca”
cells Ca” influx through L-type
Ca” stores serve to amplify the initial Ca”