TY - JOUR
T1 - Cardiac myocytes and local signaling in nano-domains
AU - Winslow, Raimond L.
AU - Greenstein, Joseph L.
N1 - Funding Information:
Supported by National Institutes of Health grants HL081427 , HL087345 , HL105239 , and HL1052160 .
PY - 2011/10
Y1 - 2011/10
N2 - It is well known that calcium-induced calcium-release in cardiac myocytes takes place in spatially restricted regions known as dyads, where discrete patches of junctional sarcoplasmic reticulum tightly associate with the t-tubule membrane. The dimensions of a dyad are so small that it contains only a few Ca 2+ ions at any given time. Ca 2+ signaling in the dyad is therefore noisy, and dominated by the Brownian motion of Ca 2+ ions in a potential field. Remarkably, from this complexity emerges the integrated behavior of the myocyte in which, under normal conditions, precise control of Ca 2+ release and muscle contraction is maintained over the life of the cell. This is but one example of how signal processing within the cardiac myocyte and other cells often occurs in small " nano-domains" where proteins and protein complexes interact at spatial dimensions on the order of ∼1-10 nm and at time-scales on the order of nanoseconds to perform the functions of the cell. In this article, we will review several examples of local signaling in nano-domains, how it contributes to the integrative behavior of the cardiac myocyte, and present computational methods for modeling signal processing within these domains across differing spatio-temporal scales.
AB - It is well known that calcium-induced calcium-release in cardiac myocytes takes place in spatially restricted regions known as dyads, where discrete patches of junctional sarcoplasmic reticulum tightly associate with the t-tubule membrane. The dimensions of a dyad are so small that it contains only a few Ca 2+ ions at any given time. Ca 2+ signaling in the dyad is therefore noisy, and dominated by the Brownian motion of Ca 2+ ions in a potential field. Remarkably, from this complexity emerges the integrated behavior of the myocyte in which, under normal conditions, precise control of Ca 2+ release and muscle contraction is maintained over the life of the cell. This is but one example of how signal processing within the cardiac myocyte and other cells often occurs in small " nano-domains" where proteins and protein complexes interact at spatial dimensions on the order of ∼1-10 nm and at time-scales on the order of nanoseconds to perform the functions of the cell. In this article, we will review several examples of local signaling in nano-domains, how it contributes to the integrative behavior of the cardiac myocyte, and present computational methods for modeling signal processing within these domains across differing spatio-temporal scales.
KW - Cardiac myocyte
KW - Computational modeling
KW - Excitation-contraction coupling
KW - Local signaling domain
KW - Multi-scale modeling
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U2 - 10.1016/j.pbiomolbio.2011.06.005
DO - 10.1016/j.pbiomolbio.2011.06.005
M3 - Review article
C2 - 21718716
AN - SCOPUS:80053586910
SN - 0079-6107
VL - 107
SP - 48
EP - 59
JO - Progress in Biophysics and Molecular Biology
JF - Progress in Biophysics and Molecular Biology
IS - 1
ER -