%0 Journal Article %1 Schr_1998_969 %A Schr�der, F. %A Handrock, R. %A Beuckelmann, D. J. %A Hirt, S. %A Hullin, R. %A Priebe, L. %A Schwinger, R. H. %A Weil, J. %A Herzig, S. %D 1998 %J Circulation %K 8-Bromo 9737516 AMP, Adenosine Atria, Barium, Calcineurin, Calcium Calcium, Cardiomyopathies, Cardiomyopathy, Cell Cells, Channel Channels, Comparative Congestive, Cultured, Cyclic Cyclosporine, Dilated, Factors, Failure, Gating, Gov't, Heart Heart, Humans, Ion Ischemia, Kinetics, L-Type, Line, Membrane Monophosphate, Muscle Myocardia, Non-U.S. P.H.S., Potentials, Probability, Proteins, Recombinant Reference Research Study, Support, Time U.S. Values, Ventricles, l %N 10 %P 969--976 %T Increased availability and open probability of single L-type calcium channels from failing compared with nonfailing human ventricle. %U http://circ.ahajournals.org/cgi/content/full/98/10/969 %V 98 %X BACKGROUND: The role of the L-type calcium channel in human heart failure is unclear, on the basis of previous whole-cell recordings. METHODS AND RESULTS: We investigated the properties of L-type calcium channels in left ventricular myocytes isolated from nonfailing donor hearts (n= 16 cells) or failing hearts of transplant recipients with dilated (n=9) or ischemic (n=7) cardiomyopathy. The single-channel recording technique was used (70 mmol/L Ba2+). Peak average currents were significantly enhanced in heart failure (38.2+/-9.3 fA) versus nonfailing control hearts (13.2+/-4.5 fA, P=0.02) because of an elevation of channel availability (55.9+/-6.7\% versus 26.4+/-5.3\%, P=0.001) and open probability within active sweeps (7.36+/-1.51\% versus 3.18+/-1.33\%, P=0.04). These differences closely resembled the effects of a cAMP-dependent stimulation with 8-Br-cAMP (n= 11). Kinetic analysis of the slow gating shows that channels from failing hearts remain available for a longer time, suggesting a defect in the dephosphorylation. Indeed, the phosphatase inhibitor okadaic acid was unable to stimulate channel activity in myocytes from failing hearts (n=5). Expression of calcium channel subunits was measured by Northern blot analysis. Expression of alpha1c- and beta-subunits was unaltered. Whole-cell current measurements did not reveal an increase of current density in heart failure. CONCLUSIONS: Individual L-type calcium channels are fundamentally affected in severe human heart failure. This is probably important for the impairment of cardiac excitation-contraction coupling.

@article{Schr_1998_969, abstract = {BACKGROUND: The role of the L-type calcium channel in human heart failure is unclear, on the basis of previous whole-cell recordings. METHODS {AND} RESULTS: We investigated the properties of L-type calcium channels in left ventricular myocytes isolated from nonfailing donor hearts (n= 16 cells) or failing hearts of transplant recipients with dilated (n=9) or ischemic (n=7) cardiomyopathy. The single-channel recording technique was used (70 mmol/L Ba2+). Peak average currents were significantly enhanced in heart failure (38.2+/-9.3 fA) versus nonfailing control hearts (13.2+/-4.5 fA, P=0.02) because of an elevation of channel availability (55.9+/-6.7\% versus 26.4+/-5.3\%, P=0.001) and open probability within active sweeps (7.36+/-1.51\% versus 3.18+/-1.33\%, P=0.04). These differences closely resembled the effects of a c{AMP}-dependent stimulation with 8-Br-c{AMP} (n= 11). Kinetic analysis of the slow gating shows that channels from failing hearts remain available for a longer time, suggesting a defect in the dephosphorylation. Indeed, the phosphatase inhibitor okadaic acid was unable to stimulate channel activity in myocytes from failing hearts (n=5). Expression of calcium channel subunits was measured by Northern blot analysis. Expression of alpha1c- and beta-subunits was unaltered. Whole-cell current measurements did not reveal an increase of current density in heart failure. {CONCLUSIONS}: Individual L-type calcium channels are fundamentally affected in severe human heart failure. This is probably important for the impairment of cardiac excitation-contraction coupling.}, added-at = {2009-06-03T11:20:58.000+0200}, author = {Schr�der, F. and Handrock, R. and Beuckelmann, D. J. and Hirt, S. and Hullin, R. and Priebe, L. and Schwinger, R. H. and Weil, J. and Herzig, S.}, biburl = {https://www.bibsonomy.org/bibtex/205673ccebee0a0008e24ca2614f5918b/hake}, description = {The whole bibliography file I use.}, file = {Schr_1998_969.pdf:Schr_1998_969.pdf:PDF}, interhash = {1d35ee78e833fc2a2734b7e98eea695e}, intrahash = {05673ccebee0a0008e24ca2614f5918b}, journal = {Circulation}, key = 147, keywords = {8-Bromo 9737516 AMP, Adenosine Atria, Barium, Calcineurin, Calcium Calcium, Cardiomyopathies, Cardiomyopathy, Cell Cells, Channel Channels, Comparative Congestive, Cultured, Cyclic Cyclosporine, Dilated, Factors, Failure, Gating, Gov't, Heart Heart, Humans, Ion Ischemia, Kinetics, L-Type, Line, Membrane Monophosphate, Muscle Myocardia, Non-U.S. P.H.S., Potentials, Probability, Proteins, Recombinant Reference Research Study, Support, Time U.S. Values, Ventricles, l}, month = Sep, number = 10, pages = {969--976}, pmid = {9737516}, timestamp = {2009-06-03T11:21:29.000+0200}, title = {Increased availability and open probability of single L-type calcium channels from failing compared with nonfailing human ventricle.}, url = {http://circ.ahajournals.org/cgi/content/full/98/10/969}, volume = 98, year = 1998 }