%0 Journal Article %1 Zahr_2003_C1059 %A Zahradn�kov�, A. %A Dura, M. %A Gy�rke, I. %A Escobar, A. L. %A Zahradn�k, I. %A Gy�rke, S. %D 2003 %J Am. J. Physiol. Cell Physiol. %K Animals; Calcium Calcium; Cardiac; Cells, Channel Cultured; Dogs; Dose-Response Drug; Magnesium; Myocytes, Receptor Relationship, Release Ryanodine %N 5 %P C1059--C1070 %R 10.1152/ajpcell.00118.2003 %T Regulation of dynamic behavior of cardiac ryanodine receptor by Mg2+ under simulated physiological conditions. %U http://ajpcell.physiology.org/cgi/content/full/285/5/C1059 %V 285 %X Mg2+, an important constituent of the intracellular milieu in cardiac myocytes, is known to inhibit ryanodine receptor (RyR) Ca$^2+$ release channels by competing with Ca$^2+$ at the cytosolic activation sites of the channel. However, the significance of this competition for local, dynamic Ca$^2+$-signaling processes thought to govern cardiac excitation-contraction (EC) coupling remains largely unknown. In the present study, Ca$^2+$ stimuli of different waveforms (i.e., sustained and brief) were generated by photolysis of the caged Ca$^2+$ compound nitrophenyl (NP)-EGTA. The evoked RyR activity was measured in planar lipid bilayers in the presence of 0.6-1.3 mM free Mg2+ at the background of 3 mM total ATP in the presence or absence of 1 mM luminal Ca$^2+$. Mg2+ dramatically slowed the rate of activation of RyRs in response to sustained (> or =10-ms) elevations in Ca$^2+$ concentration. Paradoxically, Mg2+ had no measurable impact on the kinetics of the RyR response induced by physiologically relevant, brief (<1-ms) Ca$^2+$ stimuli. Instead, the changes in activation rate observed with sustained stimuli were translated into a drastic reduction in the probability of responses. Luminal Ca$^2+$ did not affect the peak open probability or the probability of responses to brief Ca$^2+$ signals; however, it slowed the transition to steady state and increased the steady-state open probability of the channel. Our results indicate that Mg2+ is a critical physiological determinant of the dynamic behavior of the RyR channel, which is expected to profoundly influence the fidelity of coupling between L-type Ca$^2+$ channels and RyRs in heart cells.

@article{Zahr_2003_C1059, abstract = {Mg2+, an important constituent of the intracellular milieu in cardiac myocytes, is known to inhibit ryanodine receptor (RyR) {C}a$^{2+}$ release channels by competing with {C}a$^{2+}$ at the cytosolic activation sites of the channel. However, the significance of this competition for local, dynamic {C}a$^{2+}$-signaling processes thought to govern cardiac excitation-contraction (EC) coupling remains largely unknown. In the present study, {C}a$^{2+}$ stimuli of different waveforms (i.e., sustained and brief) were generated by photolysis of the caged {C}a$^{2+}$ compound nitrophenyl (NP)-EGTA. The evoked RyR activity was measured in planar lipid bilayers in the presence of 0.6-1.3 mM free Mg2+ at the background of 3 mM total ATP in the presence or absence of 1 mM luminal {C}a$^{2+}$. Mg2+ dramatically slowed the rate of activation of RyRs in response to sustained (> or =10-ms) elevations in {C}a$^{2+}$ concentration. Paradoxically, Mg2+ had no measurable impact on the kinetics of the RyR response induced by physiologically relevant, brief (<1-ms) {C}a$^{2+}$ stimuli. Instead, the changes in activation rate observed with sustained stimuli were translated into a drastic reduction in the probability of responses. Luminal {C}a$^{2+}$ did not affect the peak open probability or the probability of responses to brief {C}a$^{2+}$ signals; however, it slowed the transition to steady state and increased the steady-state open probability of the channel. Our results indicate that Mg2+ is a critical physiological determinant of the dynamic behavior of the RyR channel, which is expected to profoundly influence the fidelity of coupling between L-type {C}a$^{2+}$ channels and RyRs in heart cells.}, added-at = {2009-06-03T11:20:58.000+0200}, author = {Zahradn�kov�, A. and Dura, M. and Gy�rke, I. and Escobar, A. L. and Zahradn�k, I. and Gy�rke, S.}, biburl = {https://www.bibsonomy.org/bibtex/25626b6a3b6ca2ac617f9a5ca86a3b076/hake}, description = {The whole bibliography file I use.}, doi = {10.1152/ajpcell.00118.2003}, file = {Zahr_2003_C1059.pdf:Zahr_2003_C1059.pdf:PDF}, institution = {Institute of Molecular Physiology and Genetics, Slovak Academy of Sciences, Vl�rska 5, 833 34 Bratislava, Slovak Republic. alexandra.zahradnikova@savba.sk}, interhash = {f8889acf97c576ac5a2b058b501943b7}, intrahash = {5626b6a3b6ca2ac617f9a5ca86a3b076}, journal = {Am. J. Physiol. Cell Physiol.}, keywords = {Animals; Calcium Calcium; Cardiac; Cells, Channel Cultured; Dogs; Dose-Response Drug; Magnesium; Myocytes, Receptor Relationship, Release Ryanodine}, month = Nov, number = 5, pages = {C1059--C1070}, pdf = {Zahr_2003_C1059.pdf}, pii = {00118.2003}, pmid = {12839831}, timestamp = {2009-06-03T11:21:38.000+0200}, title = {Regulation of dynamic behavior of cardiac ryanodine receptor by Mg2+ under simulated physiological conditions.}, url = {http://ajpcell.physiology.org/cgi/content/full/285/5/C1059}, volume = 285, year = 2003 }