Sensitivity of rabbit ventricular action potential and Ca²⁺ dynamics to small variations in membrane currents and ion diffusion coefficients.
Sensitivity of rabbit ventricular action potential and Ca²⁺ dynamics to small variations in membrane currents and ion diffusion coefficients.
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DOI：
10.1155/2013/565431
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发表时间：
2013
影响因子：
--
通讯作者：
Michailova A
中科院分区：
文献类型：
--
作者：
Lo YH;Peachey T;Abramson D;McCulloch A;Michailova A
Little is known about how small variations in ionic currents and Ca2+ and Na+ diffusion coefficients impact action potential and Ca2+ dynamics in rabbit ventricular myocytes. We applied sensitivity analysis to quantify the sensitivity of Shannon et al. model (Biophys. J., 2004) to 5%–10% changes in currents conductance, channels distribution, and ion diffusion in rabbit ventricular cells. We found that action potential duration and Ca2+ peaks are highly sensitive to 10% increase in L-type Ca2+ current; moderately influenced by 10% increase in Na+-Ca2+ exchanger, Na+-K+ pump, rapid delayed and slow transient outward K+ currents, and Cl− background current; insensitive to 10% increases in all other ionic currents and sarcoplasmic reticulum Ca2+ fluxes. Cell electrical activity is strongly affected by 5% shift of L-type Ca2+ channels and Na+-Ca2+ exchanger in between junctional and submembrane spaces while Ca2+-activated Cl−-channel redistribution has the modest effect. Small changes in submembrane and cytosolic diffusion coefficients for Ca2+, but not in Na+ transfer, may alter notably myocyte contraction. Our studies highlight the need for more precise measurements and further extending and testing of the Shannon et al. model. Our results demonstrate usefulness of sensitivity analysis to identify specific knowledge gaps and controversies related to ventricular cell electrophysiology and Ca2+ signaling.
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影响因子：
4
作者：
Kekenes-Huskey PM;Cheng Y;Hake JE;Sachse FB;Bridge JH;Holst MJ;McCammon JA;McCulloch AD;Michailova AP
通讯作者：
Michailova AP
影响因子：
7.3
作者：
Farkas, A. S.;Acsai, K.;Farkas, A.
通讯作者：
Farkas, A.
影响因子：
3.4
作者：
CANNELL, MB;ALLEN, DG
通讯作者：
ALLEN, DG
影响因子：
2.4
作者：
Hatano, Asuka;Okada, Jun-ichi;Sugiura, Seiryo
通讯作者：
Sugiura, Seiryo
影响因子：
3.4
作者：
Aslanidi, Oleg V.;Sleiman, Rakan N.;Zhang, Henggui
通讯作者：
Zhang, Henggui