Regulation of [gamma-3H]aminobutyric acid transport by Ca2+ in isolated synaptic plasma membrane vesicles.
We studied the effect of Ca2+ on the transport of the gamma-aminobutyric acid (GABA) by synaptic plasma membrane (SPM) vesicles isolated from sheep brain cortex and observed that intravesicular Ca2+ inhibits the [3H]GABA accumulation in a concentration-dependent manner. This inhibitory effect of Ca2+ exhibited two distinct components: one in the micromolar range of Ca2+ concentration, and the other in the millimolar range. Previous EGTA washing of the membranes, or incorporation of trifluoperazine into the vesicular space reduced the inhibitory action of Ca2+, particularly at low Ca2+ (1-5 microM). Okadaic acid (1 microM) also relieved the Ca2+ inhibition at low, but not at high Ca2+ concentrations (1 mM), whereas the calpain inhibitor I did not alter the effect of the low Ca2+, but it partially reduced (approximately 28%) the effect of Ca2+ in the millimolar range. The results indicate that the GABA transporter is regulated by low Ca2+ concentration (microM) and probably its effect is mediated by the (Ca2+ x calmodulin)-stimulated phosphatase 2B (calcineurin). In contrast, the GABA uptake inhibition observed at high Ca2+ concentrations (1 mM) is less specific, and probably it is partially related to the proteolytic activity of membrane bound calpain II.[1]References
- Regulation of [gamma-3H]aminobutyric acid transport by Ca2+ in isolated synaptic plasma membrane vesicles. Gonçalves, P.P., Carvalho, A.P., Vale, M.G. Brain Res. Mol. Brain Res. (1997) [Pubmed]
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