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Title: Increased catecholamine secretion contributes to hypertension in TRPM4-deficient mice
Authors: Mathar, Ilka ×
Vennekens, Rudi
Meissner, Marcel
Kees, Frieder
Van der Mieren, Gerry
Camacho Londoño, Juan E
Uhl, Sebastian
Voets, Thomas
Hummel, Björn
van den Bergh, An
Herijgers, Paul
Nilius, Bernd
Flockerzi, Veit
Schweda, Frank
Freichel, Marc #
Issue Date: Sep-2010
Publisher: American Society for Clinical Investigation
Series Title: Journal of Clinical Investigation vol:120 issue:9 pages:3267-3279
Abstract: Hypertension is an underlying risk factor for cardiovascular disease. Despite this, its pathogenesis remains unknown in most cases. Recently, the transient receptor potential (TRP) channel family was associated with the development of several cardiovascular diseases linked to hypertension. The melastatin TRP channels TRPM4 and TRPM5 have distinct properties within the TRP channel family: they form nonselective cation channels activated by intracellular calcium ions. Here we report the identification of TRPM4 proteins in endothelial cells, heart, kidney, and chromaffin cells from the adrenal gland, suggesting that they have a role in the cardiovascular system. Consistent with this hypothesis, Trpm4 gene deletion in mice altered long-term regulation of blood pressure toward hypertensive levels. No changes in locomotor activity, renin-angiotensin system function, electrolyte and fluid balance, vascular contractility, and cardiac contractility under basal conditions were observed. By contrast, inhibition of ganglionic transmission with either hexamethonium or prazosin abolished the difference in blood pressure between Trpm4-/- and wild-type mice. Strikingly, plasma epinephrine concentration as well as urinary excretion of catecholamine metabolites were substantially elevated in Trpm4-/- mice. In freshly isolated chromaffin cells, lack of TRPM4 was shown to cause markedly more acetylcholine-induced exocytotic release events, while neither cytosolic calcium concentration, size, nor density of vesicles were different. We therefore conclude that TRPM4 proteins limit catecholamine release from chromaffin cells and that this contributes to increased sympathetic tone and hypertension.
URI: 
ISSN: 0021-9738
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Ion Channel Research (VIB-KU Leuven Center for Brain & Disease Research)
Experimental Cardiac Surgery (-)
Department of Cellular and Molecular Medicine - miscellaneous
× corresponding author
# (joint) last author

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