Delayed restoration of Mg²⁺content and transport in liver cells following ethanol withdrawal

Abstract

Liver cells from rats chronically fed a Lieber-De Carli diet for 3 wk presented a marked decreased in tissue Mg(2+) content and an inability to extrude Mg(2+) into the extracellular compartment upon stimulation with catecholamine, isoproterenol, or cell-permeant cAMP analogs. This defect in Mg(2+) extrusion was observed in both intact cells and purified liver plasma membrane vesicles. Inhibition of adrenergic or cAMP-mediated Mg(2+) extrusion was also observed in freshly isolated hepatocytes from control rats incubated acutely in vitro with varying doses of ethanol (EtOH) for 8 min. In this model, however, the defect in Mg(2+) extrusion was observed in intact cells but not in plasma membrane vesicles. In the chronic model, upon removal of EtOH from the diet hepatic Mg(2+) content and extrusion required approximately 10 days to return to normal level both in isolated cells and plasma membrane vesicles. In hepatocytes acutely treated with EtOH for 8 min, more than 60 min were necessary for Mg(2+) content and extrusion to recover and return to the level observed in EtOH-untreated cells. Taken together, these data suggest that in the acute model the defect in Mg(2+) extrusion is the result of a limited refilling of the cellular compartment(s) from which Mg(2+) is mobilized upon adrenergic stimulation rather than a mere defect in adrenergic cellular signaling. The chronic EtOH model, instead, presents a transient but selective defect of the Mg(2+) extrusion mechanisms in addition to the limited refilling of the cellular compartments.

Effect of acute and prolonged alcohol administration on Mg2+ homeostasis in cardiac cells

“…Cardiac cells from animals exposed to alcohol for 3 weeks require 10 days or so to restore their cellular Mg 2+ levels to pre-ethanol levels (Table 2). A similar time course has been observed in liver cells (Torres et al, 2009) and is related to the defective translocation of PKCε from cytoplasm to cell membrane (Torres et al, 2010). …”

“…On the other hand, ethanol inhibits the Mg 2+ entry mechanism for more than 45 min after alcohol removal (Torres, Konopnika, Berti-Mattera, Liedtke, & Romani, 2010), de facto hampering the restoration of proper Mg 2+ homeostasis. Similar effects occur on prolonged bases in hepatocytes from animals exposed to alcohol in the diet for 3 weeks (Torres, Cefaratti, Berti-Mattera, & Romani, 2009; Young, Cefaratti, & Romani, 2003). …”

Defective Translocation of PKCε in EtOH‐Induced Inhibition of Mg2+ Accumulation in Rat Hepatocytes

“…Cells were scraped, and the acid mixture was transferred to microfuge tubes for overnight digestion. Following sedimentation of the denatured protein at 2,000× g for 5 minutes in a Beckman J‐6B, the Mg 2+ content in the acid extract was measured by AAS (Tessman and Romani, 1998; Torres et al., 2009; Young et al., 2003, 2007).…”

“…A larger and more persistent decrease in hepatic Mg 2+ and ATP contents have been observed in rats receiving EtOH in the diet for 3 to 4 weeks (Young et al., 2003). In this chronic model of EtOH administration, approximately 12 days are necessary for hepatic Mg 2+ content to return to basal level upon withdrawal of EtOH from the diet (Torres et al., 2009).…”

Ethanol Effect on BK Channels is Modulated by Magnesium

“…Although at the cellular level, this would have various consequences; at the systemic level, the overall effect can be interpreted as another mechanism for tolerance in habitual (or chronic) EtOH drinkers. Given that while in occasional drinkers, the Mg 2+ levels would recover shortly after cessation of EtOH consumption, in habitual drinkers, the Mg 2+ levels would remain low for extended periods (Eckardt et al., ; Poikolainen and Alho, ; Torres et al., ).…”