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...

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Veröffentlicht in:The Journal of physiology 2004-09, Vol.559 (3), p.761-776
Hauptverfasser: Gwanyanya, Asfree, Amuzescu, Bogdan, Zakharov, Sergey I., Macianskiene, Regina, Sipido, Karin R., Bolotina, Victoria M., Vereecke, Johan, Mubagwa, Kanigula
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Sprache:eng
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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 10–20 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+ ≫ Mg 2+ = Ca 2+ ≈ 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= 0.4–0.5). 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