Body Temperature Change May Trigger Cardiac Death

A mutant cardiac sodium channel gene could explain why changes in body temperature trigger cardiac arrhythmia leading to sudden death, according to a new study.

Researchers at Simon Fraser University (SFU; Burnaby, Canada) found that cardiac arrhythmias are often associated with mutations in SCN5A, a gene that encodes the cardiac paralog of the voltage-gated sodium channel NaV 1.5. They therefore measured biophysical properties of the WT, E1784K, and R1193Q mutant gene variations that code NaV 1.5—including the sodium channels' voltage-dependent and kinetic properties--at three different temperatures: 10 °C, 22 °C, and 34 °C. The results showed that the E1784K mutant NaV 1.5 channel is more thermosensitive than either the WT or R1193Q channels.

They found that when normal body temperature goes up during exercise, or goes down during sleep, the affected protein no longer functions normally. The disrupted protein function affects the sodium channels, causing cardiac electrical signal to become erratic, triggering an arrhythmia. While the gene mutation is very rare, it can produce deadly results when combined with other arrhythmia triggers, for example changes in blood Ph that occur normally as a by-product of exercise and sleep, particularly sleep apnea. The study was published on July 1, 2015, in the Journal of Physiology.

“An earlier study of ours found that temperature changes are a trigger for some seizure disorders; we imagined that cardiac arrhythmias are like seizures, and wondered whether they might share the same triggers,” said lead author Prof. Peter Ruben, PhD, of the department of biomedical physiology and kinesiology. “The electrical signal behind muscle contraction is produced by tiny protein molecules in the membrane of our heart cells. Temperature fluctuations modify the way all proteins behave, but some DNA mutations can make proteins especially sensitive to changes in temperature.”

According to the researchers, the new knowledge could encourage people to examine their family histories and, if sudden cardiac death is part of that family history, or if they suffer from unexplained fainting, they can seek medical advice. Through a combination of electrocardiograms (ECGs), genetic screening, and lifestyle management, some tragic deaths caused by cardiac arrhythmia may be prevented.

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