Neuroscience 2001 Abstract
| Presentation Number: | 804.14 |
|---|---|
| Abstract Title: | ZINC EXPOSURE INHIBITS NEURONAL NA+-K+ ATPASE IN HOMOGENATES AND INCREASES INTRACELLULAR FREE SODIUM IN CELL CULTURE.<sup></sup><sup></sup><sup></sup><sup></sup> |
| Authors: |
Canzoniero, L. M. T.*1
; Blanco, G. V.2
; Manzerra, P.1
; Wang, X. Q.1
; Yu, S. P.1
; Choi, D. W.1
1Neurology and Center for the Study of Nervous System Injury, Washington University , St Louis, MO 2Molecular and Integrative Physiology, University of Kansas, Kansas City, KS |
| Primary Theme and Topics |
Synaptic Transmission and Excitability - Neurotransmitters -- Other |
| Secondary Theme and Topics | Neurological and Psychiatric Conditions<br />- Neurodegenerative Disorders<br />-- Excitatory amino acids: exicotoxicity and cell death |
| Session: |
804. Neurotransmitters: other I Poster |
| Presentation Time: | Wednesday, November 14, 2001 2:00 PM-3:00 PM |
| Location: | Exhibit Hall D-7 |
| Keywords: | cortical neurons, optical imaging , chelators, neuronal death |
Zinc is released into the synaptic cleft with synaptic activity, reaching 10 or even 100 μM concentrations. We previously reported that brief exposure to 50 μZn2+ could upregulate NMDA receptors via activation of Src kinase (Manzerra et al, SFN 2000). A plausible mechanism for this upregulation is inhibition of the membrane Na+ - K+ ATPase (Hexum, Biochem Pharmacol 23: 3441- 47, 1974), given recent evidence that increased intracellular sodium level ([Na+]i ) and Src kinase can act in concert to upregulate NMDA receptors (Yu and Salter, Nature 396:469-74, 1998).
Addition of 50 μM Zn2+ to the bathing medium for 5 min caused a progressive increase in [Na+]i in mouse cortical neurons loaded with SBFI, comparable to that produced by ouabain. Furthermore, we demonstrated that 5 min exposure to Zn2+ reduced Na+ - K+ ATPase activity in homogenates obtained from near-pure cortical neurons in a Zn2+ dose-dependent manner (IC50 about 50 μM). More prolonged exposure to Zn2+ (50μM, 20 min) blocked about 70% of the Na+ - K+ ATPase activity, after which pump activity could be restored by addition of the Zn2+ chelator TPEN (50 μM). These observations support the hypothesis that synaptically-released Zn2+ may reversibly inhibit the neuronal membrane Na+ - K+ ATPase, leading to alterations in postsynaptic neuronal behavior including NMDA receptor upregulation. Under pathological conditions, this mechanism may contribute to neuronal death.
Addition of 50 μM Zn2+ to the bathing medium for 5 min caused a progressive increase in [Na+]i in mouse cortical neurons loaded with SBFI, comparable to that produced by ouabain. Furthermore, we demonstrated that 5 min exposure to Zn2+ reduced Na+ - K+ ATPase activity in homogenates obtained from near-pure cortical neurons in a Zn2+ dose-dependent manner (IC50 about 50 μM). More prolonged exposure to Zn2+ (50μM, 20 min) blocked about 70% of the Na+ - K+ ATPase activity, after which pump activity could be restored by addition of the Zn2+ chelator TPEN (50 μM). These observations support the hypothesis that synaptically-released Zn2+ may reversibly inhibit the neuronal membrane Na+ - K+ ATPase, leading to alterations in postsynaptic neuronal behavior including NMDA receptor upregulation. Under pathological conditions, this mechanism may contribute to neuronal death.
Supported by NIH NINDS grant NS 30337 (DWC).
Sample Citation:
[Authors]. [Abstract Title]. Program No. XXX.XX. 2001 Neuroscience Meeting Planner. San Diego, CA: Society for Neuroscience, 2001. Online.
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