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Small animal species (e.g. mouse) have a faster heart rate than large animal species (e.g. human). We have looked for the reason from the functional level to the gene level in the human, rabbit, rat and mouse using a ‘metaanalysis’ approach. For example, review of the literature shows that, in isolated sinus node cells, the spontaneous rate is 4.6× faster and the action potential is 2.4 × shorter in mouse than in human. Although data on ionic currents are limited, data suggests that the density of the funny current (If) is ∼5× higher in mouse than in human, (Q10 of 1.38 was used to correct temperature differences among studies). Data on ion channel mRNA expression (qPCR) in the sinus node for the four species were collected from different research groups. To compare data, we either normalised to the Nav1.5 mRNA level (in atrial muscle) or the Cav1.2 mRNA level (in sinus node). Although different housekeeper genes were used (18S, 28S, HPRT), comparison of different data sets on the same tissue but with different housekeeper genes suggests that this is unimportant. In the sinus node, many ion channels were more highly expressed in mouse than in human, for example, HCN1 (by 18× partly responsible for If), HCN2 (by 26× partly responsible for If), HCN4 (by 7× partly responsible for If), Cav3.1 (by 16× responsible for the T-type Ca2+ current, Icu.t), RyR2 (by 6x; Ca2+-handling molecule) and SERCA2 (by 70x; Ca2+-handling molecule). It is concluded that the mouse heart rate is faster, because sinus node ion channel expression is higher in mouse.

Comparison of Ion Channel Gene Expression in the Sinus Node of the Human, Rabbit, Rat and Mouse