When the clock strikes: Modeling the relation between circadian rhythms and cardiac arrhythmias

Seenivasan, Pavithraa and Menon, Shakti N and Sridhar, S and Sinha, Sitabhra (2016) When the clock strikes: Modeling the relation between circadian rhythms and cardiac arrhythmias. In: 27th IUPAP Conference on Computational Physics (CCP), DEC 02-05, 2015, Guwahati, INDIA.

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Abstract

It has recently been observed that the occurrence of sudden cardiac death has a close statistical relationship with the time of day, viz., ventricular fibrillation is most likely to occur between 12am-6am, with 6pm-12am being the next most likely period. Consequently there has been significant interest in understanding how cardiac activity is influenced by the circadian clock, i.e., temporal oscillations in physiological activity with a period close to 24 hours and synchronized with the day-night cycle. Although studies have identified the genetic basis of circadian rhythm at the intracellular level, the mechanisms by which they influence cardiac pathologies are not yet fully understood. Evidence has suggested that diurnal variations in the conductance properties of ion channel proteins that govern the excitation dynamics of cardiac cells may provide the crucial link. In this paper, we investigate the relationship between the circadian rhythm as manifested in modulations of ion channel properties and the susceptibility to cardiac arrhythmias by using a mathematical model that describes the electrical activity in ventricular tissue. We show that changes in the channel conductance that lead to extreme values for the duration of action potentials in cardiac cells can result either in abnormally high-frequency reentrant activity or spontaneous conduction block of excitation waves. Both phenomena increase the likelihood of wavebreaks that are known to initiate potentially life threatening arrhythmias. Thus, disruptive cardiac excitation dynamics are most likely to occur in time-intervals of the day-night cycle during which the channel properties are closest to these extreme values, providing an intriguing relation between circadian rhythms and cardiac pathologies.

Item Type:	Conference Proceedings
Series.:	Journal of Physics Conference Series
Additional Information:	Copy right for this article belongs to the IOP PUBLISHING LTD, DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND
Keywords:	CARDIOVASCULAR-DISEASE; GENE-EXPRESSION; RISK-FACTORS; TISSUE; REPOLARIZATION; CARDIOMYOCYTE; MECHANISM; FREQUENCY; REENTRY; PROTEIN
Department/Centre:	Division of Biological Sciences > Molecular Biophysics Unit
Date Deposited:	09 Feb 2017 05:49
Last Modified:	09 Feb 2017 05:49
URI:	http://eprints.iisc.ac.in/id/eprint/56234

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