Abstract
We have monitored real-time alterations in [Ca2+]i in fluo-3-loaded cerebellar granule neurons exposed to domoate, and ascertained the influence of pharmacological blockers of various Ca2+ entry pathways on intracellular Ca2+ accumulation, excitatory amino acid (EAA) release and neuronal death. Domoate produced a rapid and concentration-dependent increase in [Ca2+]i, the magnitude of which correlated closely with the severity of neuron loss. The increase in [Ca2+]i was derived from activation of NMDA receptors, L-type voltage-sensitive calcium channels (VSCC) and the reversed mode of operation of the Na+/Ca2+ exchanger. When the level of neuroprotection conferred by pharmacological manipulation of these calcium entry pathways was regressed with the corresponding reductions in [Ca2+]i load, it was observed that neuronal vulnerability is controlled preferentially by NMDA receptors. This observation is consistent with our previous study of brevetoxin-induced autocrine excitotoxicity and with the source specificity hypothesis of others [J. Neurochem. 71 (1998) 2349], which suggests that elevation of [Ca2+]i in the vicinity of the NMDA receptor ion channel activates processes leading to neuronal death.
| Original language | English |
|---|---|
| Pages (from-to) | 20-29 |
| Number of pages | 10 |
| Journal | Brain Research |
| Volume | 924 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 4 2002 |
| Externally published | Yes |
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All Science Journal Classification (ASJC) codes
- Neuroscience(all)
Cite this
Domoic acid neurotoxicity in cultured cerebellar granule neurons is controlled preferentially by the NMDA receptor Ca2+ influx pathway. / Berman, Frederick W.; LePage, Keith T.; Murray, Thomas F.
In: Brain Research, Vol. 924, No. 1, 04.01.2002, p. 20-29.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Domoic acid neurotoxicity in cultured cerebellar granule neurons is controlled preferentially by the NMDA receptor Ca2+ influx pathway
AU - Berman, Frederick W.
AU - LePage, Keith T.
AU - Murray, Thomas F.
PY - 2002/1/4
Y1 - 2002/1/4
N2 - We have monitored real-time alterations in [Ca2+]i in fluo-3-loaded cerebellar granule neurons exposed to domoate, and ascertained the influence of pharmacological blockers of various Ca2+ entry pathways on intracellular Ca2+ accumulation, excitatory amino acid (EAA) release and neuronal death. Domoate produced a rapid and concentration-dependent increase in [Ca2+]i, the magnitude of which correlated closely with the severity of neuron loss. The increase in [Ca2+]i was derived from activation of NMDA receptors, L-type voltage-sensitive calcium channels (VSCC) and the reversed mode of operation of the Na+/Ca2+ exchanger. When the level of neuroprotection conferred by pharmacological manipulation of these calcium entry pathways was regressed with the corresponding reductions in [Ca2+]i load, it was observed that neuronal vulnerability is controlled preferentially by NMDA receptors. This observation is consistent with our previous study of brevetoxin-induced autocrine excitotoxicity and with the source specificity hypothesis of others [J. Neurochem. 71 (1998) 2349], which suggests that elevation of [Ca2+]i in the vicinity of the NMDA receptor ion channel activates processes leading to neuronal death.
AB - We have monitored real-time alterations in [Ca2+]i in fluo-3-loaded cerebellar granule neurons exposed to domoate, and ascertained the influence of pharmacological blockers of various Ca2+ entry pathways on intracellular Ca2+ accumulation, excitatory amino acid (EAA) release and neuronal death. Domoate produced a rapid and concentration-dependent increase in [Ca2+]i, the magnitude of which correlated closely with the severity of neuron loss. The increase in [Ca2+]i was derived from activation of NMDA receptors, L-type voltage-sensitive calcium channels (VSCC) and the reversed mode of operation of the Na+/Ca2+ exchanger. When the level of neuroprotection conferred by pharmacological manipulation of these calcium entry pathways was regressed with the corresponding reductions in [Ca2+]i load, it was observed that neuronal vulnerability is controlled preferentially by NMDA receptors. This observation is consistent with our previous study of brevetoxin-induced autocrine excitotoxicity and with the source specificity hypothesis of others [J. Neurochem. 71 (1998) 2349], which suggests that elevation of [Ca2+]i in the vicinity of the NMDA receptor ion channel activates processes leading to neuronal death.
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U2 - 10.1016/S0006-8993(01)03221-8
DO - 10.1016/S0006-8993(01)03221-8
M3 - Article
VL - 924
SP - 20
EP - 29
JO - Brain Research
JF - Brain Research
SN - 0006-8993
IS - 1
ER -