Magnesium-inhibited, TRPM6/7-like channel in cardiac myocytes: permeation of divalent cations and pH-mediated regulation
Cardiac tissue expresses several TRP proteins as well as a Mg 2+ -inhibited, non-selective cation current ( I MIC ) that bears many characteristics of TRP channel currents. We used the whole-cell voltage clamp technique in pig and rat ventricular myocytes to characterize the permeation, blockage pro...
Gespeichert in:
Veröffentlicht in: | The Journal of physiology 2004-09, Vol.559 (3), p.761-776 |
---|---|
Hauptverfasser: | , , , , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
Zusammenfassung: | Cardiac tissue expresses several TRP proteins as well as a Mg 2+ -inhibited, non-selective cation current ( I MIC ) that bears many characteristics of TRP channel currents. We used the whole-cell voltage clamp technique in pig and rat ventricular
myocytes to characterize the permeation, blockage properties and regulation of the cardiac I MIC channels in order to compare them with TRP channels, in particular with Mg 2+ -sensitive TRPM6 and TRPM7. We show that removing extracellular divalent cations unmasks large inward and outward monovalent
currents, which can be inhibited by intracellular Mg 2+ . Inward currents are suppressed upon replacing extracellular Na + by NMDG + . Divalent cations block monovalent I MIC and, at 10â20 m m , carry measurable currents. Their efficacy sequence in decreasing outward I MIC (Ni 2+ = Mg 2+ > Ca 2+ > Ba 2+ ) and in inducing inward I MIC (Ni 2+ â« Mg 2+ = Ca 2+ â Ba 2+ ), and their permeabilities calculated from reversal potentials are similar to those of TRPM6 and TRPM7 channels. The trivalent
cations Gd 3+ and Dy 3+ also block I MIC in a voltage-dependent manner (δ= 0.4â0.5). In addition they inhibit the inward current carried by divalent cations. I MIC is regulated by pH. Decreasing or increasing extracellular pH decreased and increased I MIC , respectively (pH 0.5 = 6.9, n H = 0.98). Qualitatively similar results were obtained on I MIC in rat basophilic leukaemia cells. These effects in cardiac myocytes were absent in the presence of high intracellular buffering
by 40 m m Hepes. Our results suggest that I MIC in cardiac cells is due to TRPM channels, most probably to TRPM6 or TRPM7 channels or to their heteromultimeres. |
---|---|
ISSN: | 0022-3751 1469-7793 |
DOI: | 10.1113/jphysiol.2004.067637 |