Copyright © 2006, European Society of Cardiology
TRPM4, a Ca2+-activated nonselective cation channel in mouse sino-atrial node cells
aInstitut de Physiologie et Biologie Cellulaires, CNRS UMR 6187, Université de Poitiers, F-86022 Poitiers Cedex, France
bInserm, U699 Equipe Avenir, Paris, F-75018, France
* Corresponding author. CNRS UMR 6187, Université de Poitiers, 40 av. du recteur Pineau, 86022 POITIERS Cedex, France. Tel.: +33 5 49 45 37 47; fax: +33 5 49 45 40 14. Email address: romain.guinamard{at}univ-poitiers.fr
Objective: A calcium-activated nonselective cation channel (NSCCa) has been recently described in several cardiac preparations. This channel is over-expressed in models of ventricular hypertrophy showing electrophysiological perturbations of heart activity, including occurrence of spontaneous activity. While these perturbations are currently attributed to a modification of the pacemaker If current activity, arguments are also in favor of participation of an NSCCa. Similarly, the NSCCa may be expressed in specialized pacemaker cells, i.e. sino-atrial node (SAN) cells. The aim of the present study was to detect such current in mouse pacemaker cells.
Methods: The inside-out configuration of the patch-clamp technique was used in freshly isolated SAN cells from adult mice. Also, RT-PCR and Western-blotting studies were used to probe for TRPM4 mRNA and protein expression.
Results: In these cells, an NSCCa activity was detected. The channel is voltage dependant with a conductance of 20.9±0.5 pS (n=11). It is equally permeable for Na+ and K+ but does not conduct Ca2+. It is activated by rise in intracellular calcium concentrations and blocked by intracellular ATP (0.5 mmol/L). Also, as a new property in cardiac cells, the channel is activated by internal application of phosphatidylinositol 4,5-bisphosphate (10 µM). It is reversibly inhibited by flufenamic acid and glibenclamide. This channel shows the hallmarks of the TRPM4 molecule, a member of the TRP melastatin subfamily. We confirm the expression of this TRP channel on SAN cells by Western blotting and RT-PCR and validate that TRPM4 is glibenclamide sensitive.
Conclusion: TRPM4 is functionally expressed in SAN cells and may be a key player in the generation and/or perturbation of heart rhythm.
KEYWORDS Arrhythmias; Ion channels; Single channel; Sinus node
Time for primary review 17 days
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