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This Article Full Text Full Text (PDF) All Versions of this Article: 575/2/443    most recent jphysiol.2006.109850v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Almulla, H. A. Articles by Flatman, P. W. Search for Related Content PubMed PubMed Citation Articles by Almulla, H. A. Articles by Flatman, P. W. Related Collections Cellular

¹ Centre for Integrative Physiology, College of Medicine and Veterinary Medicine, The University of Edinburgh, Edinburgh EH8 9XD, UK

The objective of our study was to investigate how Mg²⁺ enters mammalian cardiac cells. During this work, we found evidence for a previously undescribed route for Mg²⁺ entry, and now provide a preliminary account of its properties. Changes in Mg²⁺ influx into rat ventricular myocytes were deduced from changes in intracellular ionized Mg²⁺ concentration ([fMg²⁺]_i) measured from the fluorescence of mag-fura-2 loaded into isolated cells. Superfusion of myocytes at 37°C with Ca²⁺-free solutions with both reduced [Na⁺] and raised [Mg²⁺] caused myocytes to load with Mg²⁺. Uptake was seen with solutions containing 5 mM Mg²⁺ and 95 mM Na⁺, and increased linearly with increasing extracellular [Mg²⁺] or decreasing extracellular [Na⁺]. It was very sensitive to temperature (Q₁₀ > 9, 25--37°C), was observed even in myocytes with very low Na⁺ contents, and stopped abruptly when external [Na⁺] was returned to normal. Uptake was greatly reduced by imipramine or KB-R7943 if these were added when [fMg²⁺]_i was close to the physiological level, but was unaffected if they were applied when [fMg²⁺]_i was above 2 mM. Uptake was also reduced by depolarizing the membrane potential by increasing extracellular [K⁺] or voltage clamp to 0 mV. We suggest that initial Mg²⁺ uptake may involve several transporters, including reversed Na⁺–Mg²⁺ antiport and, depending on the exact conditions, reversed Na⁺–Ca²⁺ antiport. The ensuing rise of [fMg²⁺]_i, in conjunction with reduced [Na⁺], may then activate a new Mg²⁺ transporter that is highly sensitive to temperature, is insensitive to imipramine or KB-R7943, but is inactivated by depolarization.

(Received 16 March 2006; accepted after revision 20 June 2006; first published online 22 June 2006)
Corresponding author P. W. Flatman: Centre for Integrative Physiology, The University of Edinburgh, Hugh Robson Building, George Square, Edinburgh EH8 9XD, UK. Email: peter.flatman{at}ed.ac.uk