Characterization of Mg²⁺-regulated TRPM7-like current in human atrial myocytes.

backgroundTRPM7 (Transient Receptor Potential of the Melastatin subfamily) proteins are highly expressed in the heart, however, electrophysiological studies, demonstrating and characterizing these channels in human cardiomyocytes, are missing.

methodsWe have used the patch clamp technique to characterize the biophysical properties of TRPM7 channel in human myocytes isolated from right atria small chunks obtained from 116 patients in sinus rhythm during coronary artery and valvular surgery. Under whole-cell voltage-clamp, with Ca²⁺ and K⁺ channels blocked, currents were generated by symmetrical voltage ramp commands to potentials between -120 and +80 mV, from a holding potential of -80 mV.

resultsWe demonstrate that activated native current has dual control by intracellular Mg²⁺ (free-Mg²⁺ or ATP-bound form), and shows up- or down-regulation by its low or high levels, respectively, displaying outward rectification in physiological extracellular medium. High extracellular Mg²⁺ and Ca²⁺ block the outward current, while Gd³⁺, SpM⁴⁺, 2-APB, and carvacrol inhibit both (inward and outward) currents. Besides, divalents also permeate the channel, and the efficacy sequence, at 20 mM, was Mg²⁺>Ni²⁺>Ca²⁺>Ba²⁺>Cd²⁺ for decreasing outward and Ni²⁺>Mg²⁺>Ba²⁺≥Ca²⁺>Cd²⁺ for increasing inward currents. The defined current bears many characteristics of heterologously expressed or native TRPM7 current, and allowed us to propose that current under study is TRPM7-like. However, the time of beginning and time to peak as well steady state magnitude (range from 1.21 to 11.63 pA/pF, n(cells/patients) = 136/77) of induced TRPM7-like current in atrial myocytes from different patients showed a large variability, while from the same sample of human atria all these parameters were very homogenous. We present new information that TRPM7-like current in human myocytes is less sensitive to Mg²⁺. In addition, in some myocytes (from 24 out of 77 patients) that current was already up-regulated at membrane rupture.

conclusionsThis study provides the first electrophysiological description of TRPM7-like current in native human atrial myocytes. Less sensitivity to intracellular Mg²⁺ suggests for channel operation under physiological conditions. The TRPM7-like current up-regulation indicates the pathophysiological evidence of that current in human heart.