TY - JOUR
T1 - N-ethylmaleimide blocks depolarization-induced suppression of inhibition and enhances GABA release in the rat hippocampal slice in vitro
AU - Morishita, Wade
AU - Kirov, Sergei A.
AU - Pitler, Thomas A.
AU - Martin, Laura A.
AU - Lenz, Robert A.
AU - Alger, Bradley E.
PY - 1997
Y1 - 1997
N2 - Regulation of synaptic, GABA(A) receptor-mediated inhibition is a process of critical importance to normal brain function. Recently, we have described a phenomenon in hippocampus of a transient, yet marked, decrease in spontaneous, GABA(A) receptor-mediated IPSCs after depolarization activated Ca2+ influx into a pyramidal cell. This process, depolarization-induced suppression of inhibition (DSI), is absent in hippocampal cells that previously had been exposed to pertussis toxin in vivo, implicating a G- protein in the DSI process. To circumvent the problem that a single cell cannot be studied before and after G-protein block using the pertussis toxin pretreatment method, we have used the sulfhydryl alkylating agent N- ethylmaleimide (NEM), which blocks pertussis toxin-sensitive G-proteins, to determine whether acute inhibition of G-proteins can eliminate DSI of spontaneous IPBCs (sIPSCs). In whole-cell recordings from CA1 pyramidal cells that were first determined to express DSI, we have found that NEM does block DSI of sIPSCs. We also report that DSI of monosynaptic, evoked IPSCs is blocked by NEM, suggesting that a similar mechanism underlies both forms of DSI. It was of interest that DSI was abolished at a time when NEM had increased, not decreased, GABA transmission. Indeed, NEM greatly increased quantal GABA release by a Ca2+-independent mechanism, an observation with potentially important implications for understanding synaptic GABA release.
AB - Regulation of synaptic, GABA(A) receptor-mediated inhibition is a process of critical importance to normal brain function. Recently, we have described a phenomenon in hippocampus of a transient, yet marked, decrease in spontaneous, GABA(A) receptor-mediated IPSCs after depolarization activated Ca2+ influx into a pyramidal cell. This process, depolarization-induced suppression of inhibition (DSI), is absent in hippocampal cells that previously had been exposed to pertussis toxin in vivo, implicating a G- protein in the DSI process. To circumvent the problem that a single cell cannot be studied before and after G-protein block using the pertussis toxin pretreatment method, we have used the sulfhydryl alkylating agent N- ethylmaleimide (NEM), which blocks pertussis toxin-sensitive G-proteins, to determine whether acute inhibition of G-proteins can eliminate DSI of spontaneous IPBCs (sIPSCs). In whole-cell recordings from CA1 pyramidal cells that were first determined to express DSI, we have found that NEM does block DSI of sIPSCs. We also report that DSI of monosynaptic, evoked IPSCs is blocked by NEM, suggesting that a similar mechanism underlies both forms of DSI. It was of interest that DSI was abolished at a time when NEM had increased, not decreased, GABA transmission. Indeed, NEM greatly increased quantal GABA release by a Ca2+-independent mechanism, an observation with potentially important implications for understanding synaptic GABA release.
KW - GABA
KW - IPSC
KW - NEM
KW - hippocampus
KW - mIPSCs
KW - transmitter release
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U2 - 10.1523/jneurosci.17-03-00941.1997
DO - 10.1523/jneurosci.17-03-00941.1997
M3 - Article
C2 - 8994049
AN - SCOPUS:0031027842
SN - 0270-6474
VL - 17
SP - 941
EP - 950
JO - Journal of Neuroscience
JF - Journal of Neuroscience
IS - 3
ER -