Ageing is a significant risk factor associated with the incidence of sudden cardiac death (Priori et al. 2001). We have investigated changes in action potential duration and properties of the systolic Ca transient in sheep ventricular myocytes brought about as a result of the ageing process. Young adult sheep (18 months old) and old sheep (>7 years) were euthanased with 200 mg.kg-1 intravenous pentobarbitone. Myocytes were isolated from the mid-myocardial layer of the left ventricular free wall by collagenase digestion. Myocytes isolated from young and old animals were stimulated at a frequency of 0.25 Hz in the current clamp mode. Changes in [Ca2+]i were measured using Fluo-3 AM. Experiments were performed at both 23°C and 37oC. Data are presented as mean ± SEM from n experiments. Statistical analysis was carried out using a 2 way ANOVA or a Mann-Whitney rank sum test for non normally distributed populations.Action potential duration was increased in the old animals (p<0.01, n = 16−17 and p<0.05, n = 7 at 23 and 37°C respectively; see figure 1A). The amplitude of the systolic Ca transient was also increased in the old animals compared to the young animals (202±25 & 112±14 nM at 23°C; p<0.01, n = 12-17). The increase in the amplitude of the systolic Ca transient in old animals was associated with a decreased rate of rise of the Ca transient in these animals measured as time taken to rise between 10 and 70 % of maximum (35.3±5 & 20.5±2 ms at 23°C; p<0.001. n = 15-17). Interestingly 6 from a total of 7 cells isolated from old animals displayed abnormally shaped Ca transients when stimulated at 37°C as shown in figure 1B. This was compared to 1 out of 10 cells isolated from young animals.In summary there are marked alterations in action potential duration and Ca transient amplitude associated with ageing. Further work is required to determine if these changes are arrhythmogenic and if the abnormally shaped Ca transients recorded from cells isolated from old animals are a direct result of the ageing process or due to the increase in action potential duration.
University of Glasgow (2004) J Physiol 557P, C4
Communications: The influence of ageing on action potential duration and intracellular Ca homeostasis in sheep ventricular myocytes
K. Dibb,D.Eisner,U.Rueckschloss,G.Isenberg and A. Trafford
nit of Cardiac Physiology, University of Manchester, Manchester, UK and Department of Physiology, Martin Luther University, Halle, Germany
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Figure 1. A,representative action potentials in myocytes isolated from young (grey) and old (black) animals at 37°C. B,normalised Ca transients associated with the action potentials shown in panel A.
Where applicable, experiments conform with Society ethical requirements.