Abstract
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, ncells/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.
Highlights
TRPM7 (Transient Receptor Potential of the Melastatin subfamily) proteins are highly expressed in the heart, electrophysiological studies, demonstrating and characterizing these channels in human cardiomyocytes, are missing
Presence of TRPM7-like current in human atrial myocytes The TRPM7-like current induced by low levels of intracellular Mg2+ (Mgi2+) has been previously characterized in pig ventricular myocytes [19,20]
In part of human atrial myocytes, under the same experimental conditions, larger currents (2.16 ± 0.11 pA/pF and -0.42 ± 0.02 pA/pF, respectively, at +80 and -120 mV, nc/p = 16/11) were obtained at cell membrane rupture. This unexpected result is unlike animal data and suggests the presence of already up-regulated TRPM7-like current in human atrial myocytes
Summary
TRPM7 (Transient Receptor Potential of the Melastatin subfamily) proteins are highly expressed in the heart, electrophysiological studies, demonstrating and characterizing these channels in human cardiomyocytes, are missing. Certain features, including the implication in the entry of extracellular Mg2+ (Mgo2+) and other divalent cations [12,13], as well as a bifunctional property with ion channel and kinase activities [2,4,6] discriminate TRPM7 from a variety of other known ion channels [7,8,14,15]. These channels are constitutively open [2]. By contraries, decreased Mgi2+ (in free or ATP-bound form) up-regulates the current carried by TRPM7 channels [2,8,15,16]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
