See related article, pages 1406–1415 It is well established that heart disease can profoundly change cardiac action potentials.1 Action potential abnormalities are caused by derangements in cardiac ion channel expression and function, often called “ion channel remodeling,” that can cause serious, sometimes lethal, arrhythmias.2 The literature regarding arrhythmogenic ion channel remodeling is vast and complicated.2 A PubMed search with the single key word phrase “cardiac channel remodeling” returned 50 publications in 2007 alone, indicating a high level of research activity. A variety of cardiac disease processes, including myocardial infarction, valvular heart disease, various cardiomyopathies, arrhythmias, and hypertensive heart disease, can cause ion channel remodeling.2,3 Many of these cause cardiac hypertrophy, defined as an increase in myocardial cell mass. Because cardiomyocyte number is relatively fixed in adult life, hypertrophy is typified by an increase in cardiomyocyte size, allowing for increased heart mass with the same number of cells. Cell dimension measurements are the most direct means to characterize cardiomyocyte hypertrophy. In electrophysiological studies, cellular hypertrophy is often assessed by determining cell capacitance. The lipid bilayer (electrically resistive) cell membrane acts as a capacitor separating the electrically conducting intracellular solution from the conductive extracellular solution. Electric current passes across cardiac cell membranes to charge their capacitance, even when no current traverses ion channels. Capacitance is a function of intrinsic capacitive properties (indicated by the “dielectric constant”), the capacitive (in this case, cell membrane) surface area, and the thickness of the capacitor. The thickness and intrinsic capacitive properties of cell membranes are fairly constant, so the dominant factor determining cell capacitance is the total membrane surface area. Cell size increases with cardiac hypertrophy. Augmented cell size is accompanied by increased cell surface area, therefore inevitably increasing cell capacitance. Because hypertrophy increases cell size, increased whole-cell current amplitude is …
Read full abstract