Submitted on July 17, 2007
Accepted on August 19, 2008
Evolution of Ventricular Myocyte Electrophysiology
Barbara Rosati1, Min Dong2, Lan Cheng3, Shian-Ren Liou4, Qinghong Yan5, Ji Young Park1, Elaine Shiang1, Michael Sanguinetti3, Hong-Sheng Wang6, and David McKinnon7*
1 Physiology and Biophysics, Stony Brook University, Stony Brook, New York, United States
2 Pharmacology and Cell Biophysics, University of Cincinnati, Cincinnati, Ohio, United States
3 Physiology, University of Utah, Salt Lake City, Utah, United States
4 Neurobiology and Behavior, Stony Brook University, Stony Brook, New York, United States
5 Neurobiology and Behavior, Stony Brook University, Stony Brook , New York, United States
6 Pharmacology and cell Biophysics, University of Cincinnati, Cincinnati, Ohio, United States
7 Department of Neurobiology, SUNY at Stony Brook, Stony Brook, New York, United States; Neurobiology and Behavior, Stony Brook University, Stony Brook, New York, United States
* To whom correspondence should be addressed. E-mail: dmckinnon{at}notes.cc.sunysb.edu.
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, the importance of regulatory and structural evolution in the evolution of the electrophysiological function of cardiac myocytes was examined 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 phenomena, 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.
