%0 Journal Article %1 Matt_2004_241 %A Matthes, Jan %A J�ger, Andreas %A Handrock, Renate %A Groner, Ferdi %A Mehlhorn, Uwe %A Schwinger, Robert H %A Varadi, Gyula %A Schwartz, Arnold %A Herzig, Stefan %D 2004 %J J. Mol. Cell. Cardiol. %K 14871552 Atria, Barium, Calcineurin, Calcium Calcium, Cell Cells, Channels, Congestive, Cyclosporine, Failure, Gov't, Heart Heart, Humans, L-Type, Line, Membrane Muscle Non-U.S. P.H.S., Potentials, Proteins, Recombinant Research Support, U.S. Ventricles, %N 2 %P 241--255 %R 10.1016/j.yjmcc.2003.11.013 %T Ca$^2+$-dependent modulation of single human cardiac L-type calcium channels by the calcineurin inhibitor cyclosporine. %U http://dx.doi.org/10.1016/j.yjmcc.2003.11.013 %V 36 %X OBJECTIVE: Activity of single L-type calcium channels (LTCC) is enhanced in human failing myocardium (Circulation 98 (1998) 969.), most likely due to impaired dephosphorylation. Protein phosphatase 2B (calcineurin) has recently been shown to be involved in heart failure pathophysiology. We now focus on the regulation of single LTCC by calcineurin that were prevented by Ca$^2+$-free experimental conditions in our previous study. METHODS: Single LTCC currents were recorded in myocytes from human atrium and ventricle. Charge carriers were 70 mM Ba$^2+$, or a mixture of 30 mM Ca$^2+$ and 60 mM Ba$^2+$ to facilitate Ca$^2+$ permeation through recorded channels. The calcineurin inhibitor cyclosporine (10 microM) was used to reveal a putative role for calcineurin in regulation of LTCC. RESULTS: A mixture of Ca$^2+$ and Ba$^2+$ as charge carriers allowed for Ca$^2+$ permeation through recombinant human embryonic kidney cells and native (atrial and ventricular) human cardiac LTCC. With only Ba$^2+$ as the charge carrier, activities of both ventricular and atrial LTCC were strongly decreased by cyclosporine. In contrast, channel activity remained constant when Ca$^2+$ permeation was provided. In the presence of thapsigargin and (S)-BayK 8644, cyclosporine here even increased channel activity. CONCLUSIONS: We propose a dual cyclosporine effect on human cardiac LTCC. A non-specific inhibitory effect prevails with Ba$^2+$ permeation but can be compensated or overcome by a specific Ca$^2+$-dependent stimulation with Ca$^2+$ permeation. More complete restoration of physiological Ca$^2+$ movements (e.g., Ca$^2+$ release from sarcoplasmic reticulum) will help to define even more precisely the involvement of calcineurin in regulation of human cardiac LTCC.

@article{Matt_2004_241, abstract = {O{BJECTIVE}: Activity of single L-type calcium channels ({LTCC}) is enhanced in human failing myocardium (Circulation 98 (1998) 969.), most likely due to impaired dephosphorylation. Protein phosphatase 2B (calcineurin) has recently been shown to be involved in heart failure pathophysiology. We now focus on the regulation of single {LTCC} by calcineurin that were prevented by {C}a$^{2+}$-free experimental conditions in our previous study. METHODS: Single {LTCC} currents were recorded in myocytes from human atrium and ventricle. Charge carriers were 70 mM {B}a$^{2+}$, or a mixture of 30 mM {C}a$^{2+}$ and 60 mM {B}a$^{2+}$ to facilitate {C}a$^{2+}$ permeation through recorded channels. The calcineurin inhibitor cyclosporine (10 microM) was used to reveal a putative role for calcineurin in regulation of {LTCC}. RESULTS: A mixture of {C}a$^{2+}$ and {B}a$^{2+}$ as charge carriers allowed for {C}a$^{2+}$ permeation through recombinant human embryonic kidney cells and native (atrial and ventricular) human cardiac {LTCC}. With only {B}a$^{2+}$ as the charge carrier, activities of both ventricular and atrial {LTCC} were strongly decreased by cyclosporine. In contrast, channel activity remained constant when {C}a$^{2+}$ permeation was provided. In the presence of thapsigargin and (S)-BayK 8644, cyclosporine here even increased channel activity. {CONCLUSIONS}: We propose a dual cyclosporine effect on human cardiac {LTCC}. A non-specific inhibitory effect prevails with {B}a$^{2+}$ permeation but can be compensated or overcome by a specific {C}a$^{2+}$-dependent stimulation with {C}a$^{2+}$ permeation. More complete restoration of physiological {C}a$^{2+}$ movements (e.g., {C}a$^{2+}$ release from sarcoplasmic reticulum) will help to define even more precisely the involvement of calcineurin in regulation of human cardiac {LTCC}.}, added-at = {2009-06-03T11:20:58.000+0200}, author = {Matthes, Jan and J�ger, Andreas and Handrock, Renate and Groner, Ferdi and Mehlhorn, Uwe and Schwinger, Robert H and Varadi, Gyula and Schwartz, Arnold and Herzig, Stefan}, biburl = {https://www.bibsonomy.org/bibtex/2f5f0d9fd56a06b1926ee2d9ad5c130d8/hake}, description = {The whole bibliography file I use.}, doi = {10.1016/j.yjmcc.2003.11.013}, file = {Matt_2004_241.pdf:Matt_2004_241.pdf:PDF}, interhash = {e12a7953ec62cee9d0759da193cd24f9}, intrahash = {f5f0d9fd56a06b1926ee2d9ad5c130d8}, journal = {J. Mol. Cell. Cardiol.}, keywords = {14871552 Atria, Barium, Calcineurin, Calcium Calcium, Cell Cells, Channels, Congestive, Cyclosporine, Failure, Gov't, Heart Heart, Humans, L-Type, Line, Membrane Muscle Non-U.S. P.H.S., Potentials, Proteins, Recombinant Research Support, U.S. Ventricles,}, month = Feb, number = 2, pages = {241--255}, pii = {S0022282803003730}, pmid = {14871552}, timestamp = {2009-06-03T11:21:22.000+0200}, title = {{C}a$^{2+}$-dependent modulation of single human cardiac L-type calcium channels by the calcineurin inhibitor cyclosporine.}, url = {http://dx.doi.org/10.1016/j.yjmcc.2003.11.013}, volume = 36, year = 2004 }