Abstract:
:Beat-to-beat alternation of the action potential duration (APD) in paced cardiac cells has been linked to the onset of lethal arrhythmias. Both experimental and theoretical studies have shown that alternans at the single cell level can be caused by unstable membrane voltage (V(m)) dynamics linked to steep APD-restitution, or unstable intracellular calcium (Ca) cycling linked to high sensitivity of Ca release from the sarcoplasmic reticulum on sarcoplasmic reticulum Ca load. Identifying which of these two mechanisms is the primary cause of cellular alternans, however, has remained difficult since Ca and V(m) are bidirectionally coupled. Here, we use numerical simulations of a physiologically detailed ionic model to show that the origin of alternans can be inferred by measuring the length scales over which APD and Ca(i) alternans reverse phase during spatially discordant alternans. The main conclusion is that these scales are comparable to a few millimeters and equal when alternans is driven by APD restitution, but differ markedly when alternans is driven predominantly by unstable Ca cycling. In the latter case, APD alternans still reverses phase on a millimeter tissue scale due to electrotonic coupling, while Ca alternans reverses phase on a submillimeter cellular scale. These results show that experimentally accessible measurements of Ca(i) and V(m) in cardiac tissue can be used to shed light on the cellular origin of alternans.
journal_name
Biophys Jjournal_title
Biophysical journalauthors
Sato D,Shiferaw Y,Qu Z,Garfinkel A,Weiss JN,Karma Adoi
10.1529/biophysj.106.100982subject
Has Abstractpub_date
2007-02-15 00:00:00pages
L33-5issue
4eissn
0006-3495issn
1542-0086pii
S0006-3495(07)70920-7journal_volume
92pub_type
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