As endotherms, we mammals don't have to worry too much about fluctuating temperatures – we're pretty good at maintaining a constant body temperature no matter what the weather is outside. Ectotherms, however, aren't so lucky. For example, as temperatures drop, so do their body temperatures, with detrimental consequences, as Alexander Little explains: ‘Enzyme rates that support all physiological processes slow down and this can cause problems specifically in the muscle, where it can affect contraction strength and frequency of contraction.’ However, ectotherms, such as zebrafish, don't stop moving just because it's cold. In fact, Little, a PhD student in Frank Seebacher's group at the University of Sydney, Australia, found that cold-acclimated zebrafish actually perform better than their warmer friends. Thyroid hormone is well known for its central role in temperature regulation in mammals, therefore, ‘we were interested in whether or not it also changed muscle function in ways that could enhance swimming capacity [in zebrafish]’, says Little (p. 3514).

To investigate, Little first took his zebrafish and split them into two groups, acclimating one group to a pleasantly warm 28°C and the others to a cooler 18°C. After 3 weeks at their new temperatures, Little put his fish to a fitness test: he placed them in a swimming flume, gradually raising the rate of flow every 10 min until the fish became exhausted and were no longer able to carry on swimming. ‘It's almost like a beep test for fish’, explains Little. ‘So, it's a combination of [testing] speed and endurance and we saw that fish that are cold acclimated, compared to the warm-acclimated fish, can swim longer and at faster speeds.’ Little and Seebacher also saw that fish accustomed to cooler water beat their tails more frequently.

Next, having confirmed that his cold-acclimated fish did indeed perform better than their warmer kin, Little focused on characterising changes to the muscle. He began by looking at expression levels of several muscle-associated genes and found that a specific isoform of the sarco/endoplasmic reticulum Ca2+ ATPase, SERCA 1, was upregulated in cold-acclimated fish. Little explains that contraction of the muscle is induced when calcium ions are released from the sarcoplasmic reticulum, which indirectly allows the contractile myosin fibres to undertake their power stroke. To reset the stage for another round of contraction, the calcium needs to be pumped back into the sarcoplasmic reticulum via the ATPase SERCA. SERCA1 is the fastest of the three SERCA isoforms and Little speculates, ‘Increased SERCA1 could allow the calcium to be cleared from the muscle after contraction faster and restore the calcium to the sarcoplasmic reticulum so that the next contraction can happen more quickly.’

But was the upregulation of SERCA1 controlled by the thyroid hormone? Little treated his cold-acclimated fish with two drugs that inhibit both the production and the breakdown of the thyroid hormone into its active derivatives. Sure enough, in the hypothyroid fish, SERCA1 levels decreased, alongside a drop in their swimming performance in the beep test. What's more, when Little measured the activity of SERCA by its ability to use ATP (which it uses to power calcium pumping), he found that its activity decreased in cold-acclimated hypothyroid fish. Little was able to reinstate the SERCA1 expression levels and the superior sporting performance by providing the cold-acclimated hypothyroid fish with synthetic thyroid hormone or an active derivative of the hormone. While Little doesn't yet know exactly how the thyroid hormone upregulates SERCA1 activity, his work has shown, for the first time, that during cold acclimation the thyroid hormone can significantly alter muscles in ways that impact how fish can swim.


Thyroid hormone regulates muscle function during cold acclimation in zebrafish (Danio rerio)
J. Exp. Biol.