Actions of aluminum on voltage-activated calcium channel currents

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

1. Extracellular and intracellular effects of aluminum (Al) on voltage-activated calcium channel currents (VACCCs) of cultured rat dorsal root ganglion (DRG) neurons were investigated. Al (0.54 to 5.4 μg/ml=20-200 μM) applied extracellularly reduces VACCCs in a concentration-dependent manner. The IC50 was calculated to be 2.3 μg/ml (83 μM). All types of VACCCs were similarly reduced by Al treatment. A slight shift of the current-voltage relation to depolarized potentials was observed for higher Al concentrations (>2 μg/ml). The action of Al was found to be use dependent, with little recovery (max. 20%) after wash. 2. The effect of Al was highly pH dependent in the investigated range (pH 6.4 to 7.8). We observed a rightward shift of the concentration-response curve at pH 7.7 (IC50:3.1 μg/ml) and a leftward shift at pH 6.4 (IC50:0.56 μg/ml) compared to the concentration-response curve at pH 7.3. 3. The VACCC declined when 2.7 μg/ml Al was added to the internal solution. A steady state was reached within a few minutes. Additional extracellular application of the same concentration lead to an additional decrease of the current. These observations strongly suggest the existence of both intracellular and extracellular accessible binding sites for Al on voltage-activated calcium channels (VACCs). 4. The special characteristics of the action of Al on VACCCs, i.e., the irreversibility, use dependence, and pH dependence, as well as the additional internal binding site may contribute to its neurotoxicity.

Original languageEnglish
Pages (from-to)819-829
Number of pages11
JournalCellular and Molecular Neurobiology
Volume14
Issue number6
DOIs
Publication statusPublished - Dec 1994
Externally publishedYes

Fingerprint

Calcium Channels
Aluminum
Electric potential
Inhibitory Concentration 50
Binding Sites
Spinal Ganglia
Neurons
Rats
Recovery

Keywords

  • aluminum
  • neurotoxicity
  • pH dependence
  • voltage-activated calcium channels

ASJC Scopus subject areas

  • Neuroscience(all)
  • Genetics
  • Clinical Biochemistry
  • Cell Biology

Cite this

Actions of aluminum on voltage-activated calcium channel currents. / Platt, B.; Busselberg, Dietrich.

In: Cellular and Molecular Neurobiology, Vol. 14, No. 6, 12.1994, p. 819-829.

Research output: Contribution to journalArticle

@article{4235ce8a795b452a9870126dbe036e63,
title = "Actions of aluminum on voltage-activated calcium channel currents",
abstract = "1. Extracellular and intracellular effects of aluminum (Al) on voltage-activated calcium channel currents (VACCCs) of cultured rat dorsal root ganglion (DRG) neurons were investigated. Al (0.54 to 5.4 μg/ml=20-200 μM) applied extracellularly reduces VACCCs in a concentration-dependent manner. The IC50 was calculated to be 2.3 μg/ml (83 μM). All types of VACCCs were similarly reduced by Al treatment. A slight shift of the current-voltage relation to depolarized potentials was observed for higher Al concentrations (>2 μg/ml). The action of Al was found to be use dependent, with little recovery (max. 20{\%}) after wash. 2. The effect of Al was highly pH dependent in the investigated range (pH 6.4 to 7.8). We observed a rightward shift of the concentration-response curve at pH 7.7 (IC50:3.1 μg/ml) and a leftward shift at pH 6.4 (IC50:0.56 μg/ml) compared to the concentration-response curve at pH 7.3. 3. The VACCC declined when 2.7 μg/ml Al was added to the internal solution. A steady state was reached within a few minutes. Additional extracellular application of the same concentration lead to an additional decrease of the current. These observations strongly suggest the existence of both intracellular and extracellular accessible binding sites for Al on voltage-activated calcium channels (VACCs). 4. The special characteristics of the action of Al on VACCCs, i.e., the irreversibility, use dependence, and pH dependence, as well as the additional internal binding site may contribute to its neurotoxicity.",
keywords = "aluminum, neurotoxicity, pH dependence, voltage-activated calcium channels",
author = "B. Platt and Dietrich Busselberg",
year = "1994",
month = "12",
doi = "10.1007/BF02088687",
language = "English",
volume = "14",
pages = "819--829",
journal = "Cellular and Molecular Neurobiology",
issn = "0272-4340",
publisher = "Springer New York",
number = "6",

}

TY - JOUR

T1 - Actions of aluminum on voltage-activated calcium channel currents

AU - Platt, B.

AU - Busselberg, Dietrich

PY - 1994/12

Y1 - 1994/12

N2 - 1. Extracellular and intracellular effects of aluminum (Al) on voltage-activated calcium channel currents (VACCCs) of cultured rat dorsal root ganglion (DRG) neurons were investigated. Al (0.54 to 5.4 μg/ml=20-200 μM) applied extracellularly reduces VACCCs in a concentration-dependent manner. The IC50 was calculated to be 2.3 μg/ml (83 μM). All types of VACCCs were similarly reduced by Al treatment. A slight shift of the current-voltage relation to depolarized potentials was observed for higher Al concentrations (>2 μg/ml). The action of Al was found to be use dependent, with little recovery (max. 20%) after wash. 2. The effect of Al was highly pH dependent in the investigated range (pH 6.4 to 7.8). We observed a rightward shift of the concentration-response curve at pH 7.7 (IC50:3.1 μg/ml) and a leftward shift at pH 6.4 (IC50:0.56 μg/ml) compared to the concentration-response curve at pH 7.3. 3. The VACCC declined when 2.7 μg/ml Al was added to the internal solution. A steady state was reached within a few minutes. Additional extracellular application of the same concentration lead to an additional decrease of the current. These observations strongly suggest the existence of both intracellular and extracellular accessible binding sites for Al on voltage-activated calcium channels (VACCs). 4. The special characteristics of the action of Al on VACCCs, i.e., the irreversibility, use dependence, and pH dependence, as well as the additional internal binding site may contribute to its neurotoxicity.

AB - 1. Extracellular and intracellular effects of aluminum (Al) on voltage-activated calcium channel currents (VACCCs) of cultured rat dorsal root ganglion (DRG) neurons were investigated. Al (0.54 to 5.4 μg/ml=20-200 μM) applied extracellularly reduces VACCCs in a concentration-dependent manner. The IC50 was calculated to be 2.3 μg/ml (83 μM). All types of VACCCs were similarly reduced by Al treatment. A slight shift of the current-voltage relation to depolarized potentials was observed for higher Al concentrations (>2 μg/ml). The action of Al was found to be use dependent, with little recovery (max. 20%) after wash. 2. The effect of Al was highly pH dependent in the investigated range (pH 6.4 to 7.8). We observed a rightward shift of the concentration-response curve at pH 7.7 (IC50:3.1 μg/ml) and a leftward shift at pH 6.4 (IC50:0.56 μg/ml) compared to the concentration-response curve at pH 7.3. 3. The VACCC declined when 2.7 μg/ml Al was added to the internal solution. A steady state was reached within a few minutes. Additional extracellular application of the same concentration lead to an additional decrease of the current. These observations strongly suggest the existence of both intracellular and extracellular accessible binding sites for Al on voltage-activated calcium channels (VACCs). 4. The special characteristics of the action of Al on VACCCs, i.e., the irreversibility, use dependence, and pH dependence, as well as the additional internal binding site may contribute to its neurotoxicity.

KW - aluminum

KW - neurotoxicity

KW - pH dependence

KW - voltage-activated calcium channels

UR - http://www.scopus.com/inward/record.url?scp=0028674260&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028674260&partnerID=8YFLogxK

U2 - 10.1007/BF02088687

DO - 10.1007/BF02088687

M3 - Article

VL - 14

SP - 819

EP - 829

JO - Cellular and Molecular Neurobiology

JF - Cellular and Molecular Neurobiology

SN - 0272-4340

IS - 6

ER -