Evolution of ventricular myocyte electrophysiology

Abstract

The relative importance of regulatory versus structural evolution for the evolution of different biological systems is a subject of controversy. The primacy of regulatory evolution in the diversification of morphological traits has been promoted by many evolutionary developmental biologists. For physiological traits, however, the role of regulatory evolution has received less attention or has been considered to be relatively unimportant. To address this issue for electrophysiological systems, we examined the importance of regulatory and structural evolution in the evolution of the electrophysiological function of cardiac myocytes in mammals. In particular, two related phenomena were studied: the change in action potential morphology in small mammals and the scaling of action potential duration across mammalian phylogeny. In general, the functional properties of the ion channels involved in ventricular action potential repolarization were found to be relatively invariant. In contrast, there were large changes in the expression levels of multiple ion channel and transporter genes. For the Kv2.1 and Kv4.2 potassium channel genes, which are primary determinants of the action potential morphology in small mammals, the functional properties of the proximal promoter regions were found to vary in concordance with species-dependent differences in mRNA expression, suggesting that evolution of cis-regulatory elements is the primary determinant of this trait. Scaling of action potential duration was found to be a complex phenomenon, involving changes in the expression of a large number of channels and transporters. In this case, it is concluded that regulatory evolution is the predominant mechanism by which the scaling is achieved.

The temperature dependence of electrical excitability in fish hearts

“…For example, the APD of the brown trout ventricular myocytes is 85 ms at +25°C and only 26 ms at +35°C , whereas in the similar-sized guinea pig, the APD of ventricular myocytes is 496 and 250 ms at +35°C and +25°C, respectively (Hume and Uehara, 1985), despite the higher f H in guinea pig (resting f H of 230-300 beats min −1 ) than brown trout (maximal f H =124 beats min −1 ) (Rouslin et al, 1995;Vornanen et al, 2014). Similarly, the ventricular APD 50 of the zebrafish, a species tolerating temperatures as high as +40°C (Cortemeglia and Beitinger, 2005), is only ∼60 ms at +36°C, which is much shorter than the ventricular AP of most laboratory mammals (200-300 ms at +34°C) with comparable f H values (Rosati et al, 2008;Vornanen and Hassinen, 2016).…”

“…Indeed, in mammalian hearts, APD scales inversely with f H (and therefore with metabolic rate) -smaller animals have higher f H values and shorter APs (Rosati et al, 2008). An analogous relationship between f H and APD prevails in fish hearts under acute temperature changes; APD at the level of 50% repolarization (APD 50 ) shortens exponentially with increasing f H , giving a linear relationship when APD 50 is plotted against f H on a double log scale (Fig.…”

Electrical Excitation of the Heart in a Basal Vertebrate, the European River Lamprey (Lampetra fluviatilis)

“…AP of the vertebrate heart is characterized by a long plateau phase, which is particularly prominent in ventricles and clearly shorter in the atrial chamber (Rosati et al 2008;Haverinen and Vornanen 2009). Similarly, atrial AP of L. fluviatilis was markedly shorter than ventricular AP (see "Electrocardiogram and HR").…”

“…Electrical excitation of a cardiac myocyte is the result of concerted activity of Na 1 , K 1 , and Ca 21 ion channels generating the AP (Rosati et al 2008). It is shown that lamprey ventricular myocytes express at least I Na , I Ca , I Kr , I K1 , and I K,ATP currents, which are also present in teleost cardiac myocytes (Paajanen and Vornanen 2001;Vornanen et al 2002a;Haverinen and Vornanen 2006;Hassinen et al 2008aHassinen et al , 2008bHassinen et al , 2011.…”

Evolution of CpG island promoter function underlies changes in KChIP2 potassium channel subunit gene expression in mammalian heart

“…cis-regulatory evolution | physiological scaling L arge differences in body mass among mammals require significant changes in heart rate and ventricular action potential duration to scale cardiac physiological function to body mass (1,2). These changes in cardiac function are produced by systematic changes in myocyte electrophysiological function and in the pattern and level of expression of multiple voltage-gated ion channels and transporters (2).…”