Neuroscience 2005 Abstract
| Presentation Number: | 729.11 |
|---|---|
| Abstract Title: | Spermine potentiates hemichannel opening in cortical astrocytes. |
| Authors: |
Kucheryavykh, Y. V.*1
; Inyushin, M. Y.1
; Maldonado, H. M.1
; Burnashev, N.
; Nichols, C. G.
; Eaton, M. J.1
; Skatchkov, S. N.1
1Univ. Central del Caribe, Bayamon, Puerto Rico |
| Primary Theme and Topics |
Neural Excitability, Synapses, and Glia: Cellular Mechanisms - Synaptic Transmission -- Modulation |
| Session: |
729. Synaptic Modulation: Atypical Compounds Poster |
| Presentation Time: | Tuesday, November 15, 2005 3:00 PM-4:00 PM |
| Location: | Washington Convention Center - Hall A-C, Board # J4 |
| Keywords: | POLYAMINE, UPTAKE, CONNEXIN, ASTROGLIA |
Spermine (SPM) regulates neuronal receptors and channels and is primarily accumulated in glia, not in neurons (Glia 19(1997)171; Glia 31(2000)84). Glia lack the biosynthetic enzymes ornithine decarboxylase and spermidine synthase required for synthesis of SPM precursors (Prog. Neurobiol. 57(1999)485; SFN 2004, No. 754.15), but the mechanism of accumulation and release in glia remains unclear. Because polyamines pass through unapposed Cx38 hemichannels in a voltage-dependent manner (J. Physiol. 553(2003)95), we suggest that endogenous SPM acts as a signaling molecule between glial and neuronal cells via release and uptake through glial Cx43 hemichannels. Here we show that: (1) when glial K+ channels are blocked and extracelluar Ca2+ and Mg2+ are 2.5 and 2.0 mM, respectively, no currents were recorded in cultured rat cortical astrocytes. (2) A large non-selective ion current (1-5 nA) was activated by switching to Ca2+-Mg2+-free solution and (3) this current was blocked by many hemichannel blockers, but (4) not by 1-100 nM mefloquine (a P2X7 receptor blocker). (5) If extracellular Ca2+ and Mg2+ were increased to 1 mM, this current was depressed to about 10%. Subsequent application of exogenous SPM (1 mM) fully activated this large conductance. At a higher [SPM]out (10 mM), these currents were activated even when Ca2+ and Mg2+ were 2.5 mM, suggesting that hemichannels may be opened by SPM under physiological conditions. Finally, when external Na+ was isotonically substituted by SPM4+, robust currents were recorded and blocked by hemichannel blockers, indicating that SPM may both open and permeate hemichannels. These results strongly suggest that (i) polyamine fluxes in astrocytes are mediated by connexin hemichannels and (ii) SPM potentiates their opening.
Supported by RCMI G12-RR03035, MBRS-S06-GM50695, and NINDS and NCRR SNRP-NS39408
Sample Citation:
[Authors]. [Abstract Title]. Program No. XXX.XX. 2005 Neuroscience Meeting Planner. Washington, DC: Society for Neuroscience, 2005. Online.
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