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Magnesium‐inhibited, TRPM6/7‐like channel in cardiac myocytes: permeation of divalent cations and pH‐mediated regulation
Author(s) -
Gwanyanya Asfree,
Amuzescu Bogdan,
Zakharov Sergey I.,
Macianskiene Regina,
Sipido Karin R.,
Bolotina Victoria M.,
Vereecke Johan,
Mubagwa Kanigula
Publication year - 2004
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2004.067637
Subject(s) - divalent , chemistry , extracellular , biophysics , intracellular , trpm7 , myocyte , patch clamp , magnesium , membrane potential , ion channel , biochemistry , endocrinology , biology , receptor , organic chemistry
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.