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Cardiovasc Res. 2007 Feb 1;73(3):531-8. Epub 2006 Nov 22.

TRPM4, a Ca2+-activated nonselective cation channel in mouse sino-atrial node cells.

Author information

1
Institut de Physiologie et Biologie Cellulaires, CNRS UMR 6187, Université de Poitiers, F-86022 Poitiers Cedex, France.

Abstract

OBJECTIVE:

A calcium-activated nonselective cation channel (NSC(Ca)) 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 I(f) current activity, arguments are also in favor of participation of an NSC(Ca). Similarly, the NSC(Ca) 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 NSC(Ca) 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 microM). 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.

PMID:
17188667
DOI:
10.1016/j.cardiores.2006.11.023
[Indexed for MEDLINE]

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