Functional characterization of a Ca(2+)-activated non-selective cation channel in human atrial cardiomyocytes.
Cardiac arrhythmias, which occur in a wide variety of conditions where intracellular calcium is increased, have been attributed to the activation of a transient inward current (Iti). Iti is the result of three different [Ca]i-sensitive currents: the Na(+)-Ca2+ exchange current, a Ca(2+)-activated chloride current and a Ca(2+)-activated non-selective cationic current. Using the cell-free configuration of the patch-clamp technique, we have characterized the properties of a Ca(2+)-activated non-selective cation channel (NSC(Ca)) in freshly dissociated human atrial cardiomyocytes. In excised inside-out patches, the channel presented a linear I-V relationship with a conductance of 19 +/- 0.4 pS. It discriminated poorly among monovalent cations (Na+ and K+) and was slightly permeable to Ca2+ ions. The channel's open probability was increased by depolarization and a rise in internal calcium, for which the Kd for [Ca2+]i was 20.8 microM. Channel activity was reduced in the presence of 0.5 mM ATP or 10 microM glibenclamide on the cytoplasmic side to 22.1 +/- 16.8 and 28.5 +/- 8.6%, respectively, of control. It was also inhibited by 0.1 mM flufenamic acid. The channel shares several properties with TRPM4b and TRPM5, two members of the 'TRP melastatin' subfamily. In conclusion, the NSC(Ca) channel is a serious candidate to support the delayed after-depolarizations observed in [Ca2+] overload and thus may be implicated in the genesis of arrhythmias.
Guinamard
Romain
R
Institut de Physiologie et Biologie Cellulaires, CNRS UMR 6187, Université de Poitiers, 86022 Poitiers, France. romain.guinamard@univ-poitiers.fr
Chatelier
Aurélien
A
Demion
Marie
M
Potreau
Daniel
D
Patri
Sylvie
S
Rahmati
Mohammad
M
Bois
Patrick
P
D000255:Adenosine Triphosphate / Q000378:metabolism; D000368:Aged; D001145:Arrhythmias, Cardiac / Q000503:physiopathology*; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000502:physiology; D027682:Cation Transport Proteins / Q000502:physiology; D002412:Cations / Q000378:metabolism; D005260:Female; D006325:Heart Atria / Q000166:cytology / Q000503:physiopathology; D006801:Humans; D066298:In Vitro Techniques; D015640:Ion Channel Gating / Q000502:physiology; D007473:Ion Channels / Q000235:genetics / Q000502:physiology*; D008297:Male; D008565:Membrane Proteins / Q000502:physiology; D008875:Middle Aged; D032383:Myocytes, Cardiac / Q000502:physiology*; D018408:Patch-Clamp Techniques; D050053:TRPM Cation Channels
D015220:Calcium Channels; D027682:Cation Transport Proteins; D002412:Cations; D007473:Ion Channels; D008565:Membrane Proteins; D050053:TRPM Cation Channels; C437888:TRPM4 protein, human; C404409:TRPM5 protein, human; D000255:Adenosine Triphosphate; D002118:Calcium