%0 Journal Article %1 Pott_2005_1288 %A Pott, Christian %A Philipson, Kenneth D %A Goldhaber, Joshua I %D 2005 %J Circ. Res. %K 16293789 Action Animals, Ca, Cardiac, Contraction, Exchanger, Extramural, Gov't, Knockout, Mice, Myocardial Myocytes, N.I.H., Non-U.S. Potentials, Research Sarcolemma, Sodium-Calcium Support, lcium, %N 12 %P 1288--1295 %R 10.1161/01.RES.0000196563.84231.21 %T Excitation-contraction coupling in Na$^+$-Ca$^2+$ exchanger knockout mice: reduced transsarcolemmal Ca$^2+$ flux. %U http://dx.doi.org/10.1161/01.RES.0000196563.84231.21 %V 97 %X Cardiac-specific Na$^+$-Ca$^2+$ exchanger (NCX) knockout (KO) mice surprisingly survive into adulthood without compensatory changes in protein expression levels. To determine how cardiac function is maintained in the absence of NCX, we investigated membrane currents, intracellular Ca$^2+$, and action potentials (APs) in whole cell patch-clamped myocytes from wild-type (WT) and NCX knockout mice. There was no difference in resting Ca$^2+$ or sarcoplasmic reticular Ca$^2+$ load between KO and WT. During prolonged caffeine exposure, the decrease of the Ca$^2+$ transient was drastically slowed in KO versus WT myocytes, indicating that no alternative Ca$^2+$-extrusion mechanism is upregulated to compensate for the absence of NCX. Peak L-type Ca$^2+$ current (ICa) was reduced by 62\% in KO myocytes compared with WT. Nevertheless, the corresponding Ca$^2+$ transients were similar, implying an increase in the gain of excitation-contraction coupling in KO cells. APs recorded from KO cells repolarized more rapidly than in WT. In WT myocytes, applying a KO AP waveform voltage clamp reduced Ca$^2+$ influx via ICa by 59\% compared with WT AP waveform clamps. Again, the corresponding Ca$^2+$ transients remained similar. Our findings indicate that NCX KO myocytes limit Ca$^2+$ influx to &20\% of that in WT by reducing ICa and by abbreviating the AP. Contractility is maintained by an increase in the gain of excitation-contraction coupling resulting from both a more rapid repolarization of the AP and an as yet unidentified AP-independent mechanism.

@article{Pott_2005_1288, abstract = {Cardiac-specific {N}a$^{+}$-{C}a$^{2+}$ exchanger (NCX) knockout (KO) mice surprisingly survive into adulthood without compensatory changes in protein expression levels. To determine how cardiac function is maintained in the absence of NCX, we investigated membrane currents, intracellular {C}a$^{2+}$, and action potentials (APs) in whole cell patch-clamped myocytes from wild-type (WT) and NCX knockout mice. There was no difference in resting {C}a$^{2+}$ or sarcoplasmic reticular {C}a$^{2+}$ load between KO and WT. During prolonged caffeine exposure, the decrease of the {C}a$^{2+}$ transient was drastically slowed in KO versus WT myocytes, indicating that no alternative {C}a$^{2+}$-extrusion mechanism is upregulated to compensate for the absence of NCX. Peak L-type {C}a$^{2+}$ current (ICa) was reduced by 62\% in KO myocytes compared with WT. Nevertheless, the corresponding {C}a$^{2+}$ transients were similar, implying an increase in the gain of excitation-contraction coupling in KO cells. APs recorded from KO cells repolarized more rapidly than in WT. In WT myocytes, applying a KO AP waveform voltage clamp reduced {C}a$^{2+}$ influx via ICa by 59\% compared with WT AP waveform clamps. Again, the corresponding {C}a$^{2+}$ transients remained similar. Our findings indicate that NCX KO myocytes limit {C}a$^{2+}$ influx to &20\% of that in WT by reducing ICa and by abbreviating the AP. Contractility is maintained by an increase in the gain of excitation-contraction coupling resulting from both a more rapid repolarization of the AP and an as yet unidentified AP-independent mechanism.}, added-at = {2009-06-03T11:20:58.000+0200}, author = {Pott, Christian and Philipson, Kenneth D and Goldhaber, Joshua I}, biburl = {https://www.bibsonomy.org/bibtex/274fd2b3c405f0a4641a62ad6eeafb9d6/hake}, description = {The whole bibliography file I use.}, doi = {10.1161/01.RES.0000196563.84231.21}, file = {Pott_2005_1288.pdf:Pott_2005_1288.pdf:PDF}, interhash = {50b993546dd6aa1f3cb5fef12a78a8d1}, intrahash = {74fd2b3c405f0a4641a62ad6eeafb9d6}, journal = {Circ. Res.}, keywords = {16293789 Action Animals, Ca, Cardiac, Contraction, Exchanger, Extramural, Gov't, Knockout, Mice, Myocardial Myocytes, N.I.H., Non-U.S. Potentials, Research Sarcolemma, Sodium-Calcium Support, lcium,}, month = Dec, number = 12, pages = {1288--1295}, pii = {01.RES.0000196563.84231.21}, pmid = {16293789}, timestamp = {2009-06-03T11:21:26.000+0200}, title = {Excitation-contraction coupling in {N}a$^{+}$-{C}a$^{2+}$ exchanger knockout mice: reduced transsarcolemmal {C}a$^{2+}$ flux.}, url = {http://dx.doi.org/10.1161/01.RES.0000196563.84231.21}, volume = 97, year = 2005 }