The Journal of Neurophysiology Vol. 80 No. 2 August 1998, pp. 755-761
Copyright ©1998 The American Physiological Society

Selective Modulation of GABA_A Receptors by Aluminum

Paul Q. Trombley

Department of Biological Science, Florida State University, Tallahassee, Florida 32306-4340

Trombley, Paul Q. Selective modulation of GABA_A receptors by aluminum. J. Neurophysiol. 80: 755-761, 1998. Aluminum has been implicated in several neurodegenerative conditions including Alzheimer's disease. Because the mammalian olfactory system has an unusual capacity for the uptake and transneuronal spread of inhaled substances such as aluminum, whole cell recording techniques were used to examine the actions of aluminum on basic membrane properties and amino acid receptors on rat olfactory bulb mitral/tufted (M/T) neurons in culture. Aluminum had little direct effects on M/T neurons. Aluminum (100 µM) did not evoke a membrane current or alter action-potential shape or duration. Aluminum also had no marked effects on the family of voltage-gated membrane currents evoked by a series of 10-mV, 50-ms depolarizing steps. However, aluminum dramatically potentiated the current evoked by 30 µM -aminobutyric acid (GABA) at concentrations <100 µM. Conversely, higher concentrations of aluminum blocked the GABA-evoked current. The effects of aluminum on GABA-evoked currents were not voltage dependent. Aluminum (100 µM) equally potentiated both inward currents at 30 mV and outward currents at + 30 mV. At 300 µM, aluminum blocked both inward and outward currents to a similar extent. In some neurons, aluminum only blocked the current and potentiation was not observed. The biphasic action of aluminum on GABA-evoked currents suggests separate binding sites: a high-affinity potentiating site and a low-affinity inhibiting site. Despite its effects on GABA-evoked currents, aluminum did not alter membrane currents evoked by glutamate, N-methyl-D-aspartate, kainate, or glycine. Aluminum also did not reduce spontaneous excitatory synaptic activity, suggesting little, if any, effect on glutamate release. Although a causal role for aluminum in Alzheimer's disease and other neuropathological conditions remains controversial, it is clear that elevated aluminum concentrations in the brain are associated with a variety of cognitive impairments. The present results indicate that aluminum can alter the function of GABA_A receptors and may suggest that aluminum can contribute to cognitive impairment through disruption of inhibitory circuits.