%0 Journal Article %1 Fabe_2000_2392 %A Faber, G. M. %A Rudy, Y. %D 2000 %J Biophys. J. %K 10777735 ATPase, Action Animals, Arrhythmia, Biophysics, Calcium Calcium, Cardiovascular, Contraction, Gov't, Guinea In Ion Models, Myocardial Myocardium, Non-U.S. P.H.S., Pigs, Potassium, Potentials, Research Reticulum, Sarcoplasmic Signaling, Sodium, Support, Transport, U.S. Vitro, {N}a$^{+}$-{K}$^{+}$-Exchanging %N 5 %P 2392-404 %T Action potential and contractility changes in Na$^+$(i) overloaded cardiac myocytes: a simulation study. %U http://www.biophysj.org/cgi/content/full/78/5/2392 %V 78 %X Sodium overload of cardiac cells can accompany various pathologies and induce fatal cardiac arrhythmias. We investigate effects of elevated intracellular sodium on the cardiac action potential (AP) and on intracellular calcium using the Luo-Rudy model of a mammalian ventricular myocyte. The results are: 1) During rapid pacing, AP duration (APD) shortens in two phases, a rapid phase without Na$^+$ accumulation and a slower phase that depends on Na$^+$(i). 2) The rapid APD shortening is due to incomplete deactivation (accumulation) of I(Ks). 3) The slow phase is due to increased repolarizing currents I(NaK) and reverse-mode I(NaCa), secondary to elevated Na$^+$(i). 4) Na$^+$-overload slows the rate of AP depolarization, allowing time for greater I(Ca(L)) activation; it also enhances reverse-mode I(NaCa). The resulting increased Ca$^2+$ influx triggers a greater Ca$^2+$(i) transient. 5) Reverse-mode I(NaCa) alone can trigger Ca$^2+$ release in a voltage and Na$^+$(i)-dependent manner. 6) During I(NaK) block, Na$^+$ and Ca$^2+$ accumulate and APD shortens due to enhanced reverse-mode I(NaCa); contribution of I(K(Na)) to APD shortening is negligible. By slowing AP depolarization (hence velocity) and shortening APD, Na$^+$-overload acts to enhance inducibility of reentrant arrhythmias. Shortened APD with elevated Ca$^2+$(i) (secondary to Na$^+$-overload) also predisposes the myocardium to arrhythmogenic delayed afterdepolarizations.

@article{Fabe_2000_2392, abstract = {Sodium overload of cardiac cells can accompany various pathologies and induce fatal cardiac arrhythmias. We investigate effects of elevated intracellular sodium on the cardiac action potential (AP) and on intracellular calcium using the Luo-Rudy model of a mammalian ventricular myocyte. The results are: 1) During rapid pacing, AP duration ({APD}) shortens in two phases, a rapid phase without {N}a$^{+}$ accumulation and a slower phase that depends on [{N}a$^{+}$](i). 2) The rapid {APD} shortening is due to incomplete deactivation (accumulation) of I(Ks). 3) The slow phase is due to increased repolarizing currents I(NaK) and reverse-mode I(NaCa), secondary to elevated [{N}a$^{+}$](i). 4) {N}a$^{+}$-overload slows the rate of AP depolarization, allowing time for greater I(Ca(L)) activation; it also enhances reverse-mode I(NaCa). The resulting increased {C}a$^{2+}$ influx triggers a greater [{C}a$^{2+}$](i) transient. 5) Reverse-mode I(NaCa) alone can trigger {C}a$^{2+}$ release in a voltage and [{N}a$^{+}$](i)-dependent manner. 6) During I(NaK) block, {N}a$^{+}$ and {C}a$^{2+}$ accumulate and {APD} shortens due to enhanced reverse-mode I(NaCa); contribution of I(K(Na)) to {APD} shortening is negligible. By slowing AP depolarization (hence velocity) and shortening {APD}, {N}a$^{+}$-overload acts to enhance inducibility of reentrant arrhythmias. Shortened {APD} with elevated [{C}a$^{2+}$](i) (secondary to {N}a$^{+}$-overload) also predisposes the myocardium to arrhythmogenic delayed afterdepolarizations.}, added-at = {2009-06-03T11:20:58.000+0200}, author = {Faber, G. M. and Rudy, Y.}, biburl = {https://www.bibsonomy.org/bibtex/29527758951ad0c250a29a2f8619f8106/hake}, description = {The whole bibliography file I use.}, file = {Fabe_2000_2392.pdf:Fabe_2000_2392.pdf:PDF}, interhash = {56d9d12af7656ea334b88be6cea266ec}, intrahash = {9527758951ad0c250a29a2f8619f8106}, journal = {Biophys. J.}, key = 11, keywords = {10777735 ATPase, Action Animals, Arrhythmia, Biophysics, Calcium Calcium, Cardiovascular, Contraction, Gov't, Guinea In Ion Models, Myocardial Myocardium, Non-U.S. P.H.S., Pigs, Potassium, Potentials, Research Reticulum, Sarcoplasmic Signaling, Sodium, Support, Transport, U.S. Vitro, {N}a$^{+}$-{K}$^{+}$-Exchanging}, month = May, number = 5, pages = {2392-404}, timestamp = {2009-06-03T11:21:11.000+0200}, title = {Action potential and contractility changes in [{N}a$^{+}$](i) overloaded cardiac myocytes: a simulation study.}, url = {http://www.biophysj.org/cgi/content/full/78/5/2392}, volume = 78, year = 2000 }