%0 Journal Article %1 Yao_1998_657 %A Yao, A. %A Su, Z. %A Nonaka, A. %A Zubair, I. %A Lu, L. %A Philipson, K. D. %A Bridge, J. H. %A Barry, W. H. %D 1998 %J Circ. Res. %K 9546374 ATPase, Action Animals, Artificial, Blood Body Caffeine, Calcium Calcium, Cells, Channels, Congestive, Cultured, Diastole, Dogs, Electric Exchanger, Failure, Frames, Function, Gov't, Heart Heart, Homeostasis, Kinetics, L-Type, Mice, Myocardium, Non-U.S. Open Organ P.H.S., Pacemaker, Patch-Clamp Potentials, Pressure, Rabbits, Reading Reference Research Reticulum, Sarcoplasmic Size, Sodium, Sodium-Calcium Stimulation, Support, Systole, Techniques, Transgenic, U.S. Values, Ventricles, Ventricular Weight, {C}a$^{2+}$-Transporting %N 6 %P 657-65 %T Effects of overexpression of the Na$^+$-Ca$^2+$ exchanger on Ca$^2+$i transients in murine ventricular myocytes. %U http://circres.ahajournals.org/cgi/content/full/82/6/657 %V 82 %X We measured Ca$^2+$i and Na$^+$i in isolated transgenic (TG) mouse myocytes overexpressing the Na$^+$-Ca$^2+$ exchanger and in wild-type (WT) myocytes. In TG myocytes, the peak systolic level and amplitude of electrically stimulated (ES) Ca$^2+$i transients (0.25 Hz) were not significantly different from those in WT myocytes, but the time to peak Ca$^2+$i was significantly prolonged. The decline of ES Ca$^2+$i transients was significantly accelerated in TG myocytes. The decline of a long-duration (4-s) caffeine-induced Ca$^2+$i transient was markedly faster in TG myocytes, and Na$^+$i was identical in TG and WT myocytes, indicating that the overexpressed Na$^+$-Ca$^2+$ exchanger is functionally active. The decline of a short-duration (100-ms) caffeine-induced Ca$^2+$i transient in 0 Na$^+$/0 Ca$^2+$ solution did not differ between the two groups, suggesting that the sarcoplasmic reticulum (SR) Ca$^2+$-ATPase function is not altered by overexpression of the Na$^+$-Ca$^2+$ exchanger. There was no difference in L-type Ca$^2+$ current density in WT and TG myocytes. However, the sensitivity of ES Ca$^2+$i transients to nifedipine was reduced in TG myocytes. This maintenance of Ca$^2+$i transients in nifedipine was inhibited by Ni2+ and required SR Ca$^2+$ content, consistent with enhanced Ca$^2+$ influx by reverse Na$^+$-Ca$^2+$ exchange, and the resulting Ca$^2+$-induced Ca$^2+$ release from SR. The rate of rise of Ca$^2+$i transients in nifedipine in TG myocytes was much slower than when both the L-type Ca$^2+$ current and the Na$^+$-Ca$^2+$ exchange current function together. In TG myocytes, action potential amplitude and action potential duration at 50\% repolarization were reduced, and action potential duration at 90\% repolarization was increased, relative to WT myocytes. These data suggest that under these conditions, overexpression of the Na$^+$-Ca$^2+$ exchanger in TG myocytes accelerates the decline of Ca$^2+$i during relaxation, indicating enhanced forward Na$^+$-Ca$^2+$ exchanger function. Increased Ca$^2+$ influx also appears to occur, consistent with enhanced reverse function. These findings provide support for the physiological importance of both these modes of Na$^+$-Ca$^2+$ exchange.

@article{Yao_1998_657, abstract = {We measured [{C}a$^{2+}$]i and [{N}a$^{+}$]i in isolated transgenic (TG) mouse myocytes overexpressing the {N}a$^{+}$-{C}a$^{2+}$ exchanger and in wild-type (WT) myocytes. In TG myocytes, the peak systolic level and amplitude of electrically stimulated ({ES}) [{C}a$^{2+}$]i transients (0.25 Hz) were not significantly different from those in WT myocytes, but the time to peak [{C}a$^{2+}$]i was significantly prolonged. The decline of {ES} [{C}a$^{2+}$]i transients was significantly accelerated in TG myocytes. The decline of a long-duration (4-s) caffeine-induced [{C}a$^{2+}$]i transient was markedly faster in TG myocytes, and [{N}a$^{+}$]i was identical in TG and WT myocytes, indicating that the overexpressed {N}a$^{+}$-{C}a$^{2+}$ exchanger is functionally active. The decline of a short-duration (100-ms) caffeine-induced [{C}a$^{2+}$]i transient in 0 {N}a$^{+}$/0 {C}a$^{2+}$ solution did not differ between the two groups, suggesting that the sarcoplasmic reticulum (SR) {C}a$^{2+}$-ATPase function is not altered by overexpression of the {N}a$^{+}$-{C}a$^{2+}$ exchanger. There was no difference in L-type {C}a$^{2+}$ current density in WT and TG myocytes. However, the sensitivity of {ES} [{C}a$^{2+}$]i transients to nifedipine was reduced in TG myocytes. This maintenance of [{C}a$^{2+}$]i transients in nifedipine was inhibited by Ni2+ and required SR {C}a$^{2+}$ content, consistent with enhanced {C}a$^{2+}$ influx by reverse {N}a$^{+}$-{C}a$^{2+}$ exchange, and the resulting {C}a$^{2+}$-induced {C}a$^{2+}$ release from SR. The rate of rise of [{C}a$^{2+}$]i transients in nifedipine in TG myocytes was much slower than when both the L-type {C}a$^{2+}$ current and the {N}a$^{+}$-{C}a$^{2+}$ exchange current function together. In TG myocytes, action potential amplitude and action potential duration at 50\% repolarization were reduced, and action potential duration at 90\% repolarization was increased, relative to WT myocytes. These data suggest that under these conditions, overexpression of the {N}a$^{+}$-{C}a$^{2+}$ exchanger in TG myocytes accelerates the decline of [{C}a$^{2+}$]i during relaxation, indicating enhanced forward {N}a$^{+}$-{C}a$^{2+}$ exchanger function. Increased {C}a$^{2+}$ influx also appears to occur, consistent with enhanced reverse function. These findings provide support for the physiological importance of both these modes of {N}a$^{+}$-{C}a$^{2+}$ exchange.}, added-at = {2009-06-03T11:20:58.000+0200}, author = {Yao, A. and Su, Z. and Nonaka, A. and Zubair, I. and Lu, L. and Philipson, K. D. and Bridge, J. H. and Barry, W. H.}, biburl = {https://www.bibsonomy.org/bibtex/264b474347c20f5cf61eaef61f96cb60b/hake}, description = {The whole bibliography file I use.}, file = {Yao_1998_657.pdf:Yao_1998_657.pdf:PDF}, interhash = {621c3abfbcccd26d9850f23888a5dceb}, intrahash = {64b474347c20f5cf61eaef61f96cb60b}, journal = {Circ. Res.}, key = 33, keywords = {9546374 ATPase, Action Animals, Artificial, Blood Body Caffeine, Calcium Calcium, Cells, Channels, Congestive, Cultured, Diastole, Dogs, Electric Exchanger, Failure, Frames, Function, Gov't, Heart Heart, Homeostasis, Kinetics, L-Type, Mice, Myocardium, Non-U.S. Open Organ P.H.S., Pacemaker, Patch-Clamp Potentials, Pressure, Rabbits, Reading Reference Research Reticulum, Sarcoplasmic Size, Sodium, Sodium-Calcium Stimulation, Support, Systole, Techniques, Transgenic, U.S. Values, Ventricles, Ventricular Weight, {C}a$^{2+}$-Transporting}, month = Apr, number = 6, pages = {657-65}, timestamp = {2009-06-03T11:21:38.000+0200}, title = {Effects of overexpression of the {N}a$^{+}$-{C}a$^{2+}$ exchanger on [{C}a$^{2+}$]i transients in murine ventricular myocytes.}, url = {http://circres.ahajournals.org/cgi/content/full/82/6/657}, volume = 82, year = 1998 }