Implications of inhomogeneous distribution of IKS and IKr channels in ventricle with respect to effects of class III agents and beta-agonists

See article by Cheng et al. ([1], pages 135–147) in this issue. In this issue of Cardiovascular Research Cheng et al. [1] demonstrate that the electrical properties of single cells isolated from apex and base are different. They show that action potentials elicited at 1 Hz are 40 ms shorter in ventricular myocytes isolated from the base than in myocytes isolated from the apex. This is in line with earlier measurements of the same group. In epicardial electrograms of Langendorff-perfused rabbits hearts they found different QT intervals between ventricular apex and base [2]. Cheng et al. [1] found that tail currents in basal myocytes were larger than in apical myocytes. This indicates that delayed rectifier current I K is larger in basal cells and it explains the shorter basal action potential. Ventricular action potentials may differ regionally. Action potentials from subendocardial myocytes are longer than those from subepicardial myocytes. This difference in action potential duration is probably caused by a higher density of the transient outward current I TO in subepicardial myocytes [3–7]. Also the different rate-dependent properties of I TO between in subepi- and subendocardial myocytes may play a role [6]. Different action potential configurations also exist between left and right epicardium [8]. The most likely cause is again a different I TO density. The delayed recifier current I K is composed of two components, a rapidly activating I Kr and a slowly activating I Ks. Cheng et al. [1] found that I Kr is the largest component of I K in apical myocytes and that in basal myocytes I Ks is the largest component. These findings show that I Kr and I Ks are regionally … * Corresponding author. Tel.: +31-20-566-4644; fax: +31-20-691-9319 a.c.vanginneken{at}amc.uva.nl