TY - GEN
T1 - CaMKII-dependent activation of late INa contributes to cellular arrhythmia in a model of the cardiac myocyte
AU - Hashambhoy, Yasmin L.
AU - Winslow, Raimond L.
AU - Greenstein, Joseph L.
PY - 2011
Y1 - 2011
N2 - Cardiac voltage-gated Na channels underlie membrane depolarization during the upstroke of the action potential (AP). These channels also exhibit a late, slowly-inactivating component of current (late INa) that may be enhanced under pathological conditions such as heart failure, and may therefore promote AP prolongation and increase the likelihood of arrhythmia. Ca 2/calmodulin-dependent protein kinase II (CaMKII) functionally modifies Na channels, however it remains unclear if the CaMKII-dependent changes in late INa are a major contributor to cellular arrhythmias such as early after depolarizations (EADs). In this study we develop a model of I Na, including CaMKII-dependent effects, based on experimental measurements. The Na channel model is incorporated into a computational model of the whole myocyte which describes excitation-contraction coupling via stochastic simulation of individual Ca2 release sites. Simulations suggest that relatively small augmentation of late INa is sufficient to significantly prolong APs and lead to the appearance of EADs.
AB - Cardiac voltage-gated Na channels underlie membrane depolarization during the upstroke of the action potential (AP). These channels also exhibit a late, slowly-inactivating component of current (late INa) that may be enhanced under pathological conditions such as heart failure, and may therefore promote AP prolongation and increase the likelihood of arrhythmia. Ca 2/calmodulin-dependent protein kinase II (CaMKII) functionally modifies Na channels, however it remains unclear if the CaMKII-dependent changes in late INa are a major contributor to cellular arrhythmias such as early after depolarizations (EADs). In this study we develop a model of I Na, including CaMKII-dependent effects, based on experimental measurements. The Na channel model is incorporated into a computational model of the whole myocyte which describes excitation-contraction coupling via stochastic simulation of individual Ca2 release sites. Simulations suggest that relatively small augmentation of late INa is sufficient to significantly prolong APs and lead to the appearance of EADs.
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U2 - 10.1109/IEMBS.2011.6091155
DO - 10.1109/IEMBS.2011.6091155
M3 - Conference contribution
C2 - 22255378
AN - SCOPUS:84055199871
SN - 9781424441211
T3 - Proceedings of the Annual International Conference of the IEEE Engineering in Medicine and Biology Society, EMBS
SP - 4665
EP - 4668
BT - 33rd Annual International Conference of the IEEE Engineering in Medicine and Biology Society, EMBS 2011
PB - Institute of Electrical and Electronics Engineers Inc.
T2 - 33rd Annual International Conference of the IEEE Engineering in Medicine and Biology Society, EMBS 2011
Y2 - 30 August 2011 through 3 September 2011
ER -