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Acta Physiologica 2005; Volume 185, Supplement 649
Belgian Society for Fundamental and Clinical Physiology and Pharmacology, Autumn Meeting 2005
11/19/2005-11/19/2005
Antwerp, Belgium
REGULATION OF THE TRPM6/7-LIKE CATION CHANNEL IN CARDIAC MYOCYTES BY ATP AND PIP2
Abstract number: POSTER-13
Gwanyanya A., Vereecke1 J., Mubagwa K.
Experimental Cardiac Surgery
1Laboratory of Physiology, University of Leuven, Leuven, B-3000, Belgium
The magnesium-inhibited cation (MIC) current (IMIC) in cardiac myocytes biophysically resembles currents of heterologously expressed transient receptor potential (TRP) channels, particularly TRPM6 and TRPM7, known to be important in Mg2+ homeostasis. To understand the regulation of MIC channels in cardiac cells, we investigated the role of intracellular ATP in isolated ventricular myocytes using the whole-cell voltage-clamp technique. IMIC, studied in the presence or absence of extracellular divalent cations, was sustained for >= 50 min after patch rupture in ATP-loaded cells. In contrast, in ATP-depleted cells, IMIC exhibited rapid and complete run-down. Equimolar substitution of internal ATP by its non-hydrolysable analogue AMP-PNP failed to prevent run-down. In ATP-depleted cells, inhibition of lipid phosphatases by fluoride-vanadate-pyrophosphate prevented IMIC run-down. In contrast, under similar conditions, neither the inhibition of protein phosphatases 1, 2A, 2B, or of protein tyrosine phosphatase, nor the activation of protein kinase A (forskolin, 20 mM) or protein kinase C (phorbol 12-myristate 13-acetate, 100 nM) could prevent run-down. In ATP-loaded cells, depletion of phosphatidylinositol 4,5-bisphosphate (PIP2) by preventing its re-synthesis (wortmannin, 10 mM) induced run-down of IMIC. Finally, loading cells with exogenous PIP2 (10 mM) prevented run-down in ATP-depleted cells. These results suggest that intracellular ATP hydrolysis and PIP2, probably generated by lipid kinases, are necessary for maintaining cardiac MIC channel activity.
To cite this abstract, please use the following information:
Acta Physiologica 2005; Volume 185, Supplement 649 :POSTER-13