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J Physiol. 2000 Oct 1;528 Pt 1:39-52.

Zn2+ current is mediated by voltage-gated Ca2+ channels and enhanced by extracellular acidity in mouse cortical neurones.

Author information

1
Center for the Study of Nervous System Injury and Department of Neurology, Washington University School of Medicine, 660 S. Euclid Avenue, St Louis, MO 63110, USA.

Abstract

1. Mammalian neuronal voltage-gated Ca2+ channels have been implicated as potential mediators of membrane permeability to Zn2+. We tested directly whether voltage-gated Ca2+ channels can flux Zn2+ in whole-cell voltage-clamp recordings from cultured murine cortical neurones. 2. In the presence of extracellular Zn2+ and no Na+, K+, or other divalent cations, a small, non-inactivating, voltage-gated inward current was observed exhibiting a current-voltage relationship characteristic of high-voltage activated (HVA) Ca2+ channels. Inward current was detectable at Zn2+ levels as low as 50 microM, and both the amplitude and voltage sensitivity of the current depended upon Zn2+ concentration. This Zn2+ current was sensitive to blockade by Gd3+ and nimodipine and, to a lesser extent, by omega-conotoxin GVIA. 3. Zn2+ could permeate Ca2+ channels in the presence of Ca2+ and other physiological cations. Inward currents recorded with 2 mM Ca2+ were attenuated by Zn2+ (IC50 = 210 microM), and currents recorded with Zn2+ were unaffected by up to equimolar Ca2+ concentrations. Furthermore, the Zn2+-selective fluorescent dye Newport Green revealed a depolarisation-activated, nimodipine-sensitive Zn2+ influx into cortical neurones that were bathed in a physiological extracellular solution plus 300 microM ZnCl2. 4. Surprisingly, while lowering extracellular pH suppressed HVA Ca2+ currents, Zn2+ current amplitude was affected oppositely, varying inversely with pH with an apparent pK of 7.4. The acidity-induced enhancement of Zn2+ current was associated with a positive shift in reversal potential but no change in the kinetics or voltage sensitivity of channel activation. 5. These results provide evidence that L- and N-type voltage-gated Ca2+ channels can mediate Zn2+ entry into cortical neurones and that this entry may be enhanced by extracellular acidity.

PMID:
11018104
PMCID:
PMC2270119
DOI:
10.1111/j.1469-7793.2000.00039.x
[Indexed for MEDLINE]
Free PMC Article

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