Proceedings of The Physiological Society

University of Oxford (2011) Proc Physiol Soc 23, PC149

Poster Communications

Changes of action potential duration and intracellular calcium following a change of pacing frequency in sheep ventricular myocytes

D. J. Greensmith1, A. W. Trafford1, K. M. Dibb1, D. A. Eisner1

1. Unit of Cardiac Physiology, University of Manchester, Manchester, United Kingdom.


Action potential duration (APD) decreases following an increase in heart rate and vice versa. Changes in APD can occur with a time course of hours to days, a phenomenon known as cardiac memory. In the short term however, changes occur both rapidly (within a second) and more slowly, with a time course in the order of tens to a few hundreds of seconds. The rate constant of APD change is typically faster when rate is increased compared to when it decreases. APD changes over these time courses can also been seen in isolated ventricular myocytes. Our aim was to determine whether the slow changes in APD observed upon alteration of pacing frequency would correlate with those of intracellular calcium ([Ca2+]i). Young (~18 months) Sheep were killed in accordance with The Home Office Animal (Scientific Procedures) Act 1986 for enzymatic isolation of left ventricular mid myocardial myocytes. Myocytes loaded with the calcium indicator Fura-2 were current clamped via perforated patch and paced at 0.25 Hz, 1 Hz and 0.25 Hz sequentially, to steady state APD and Fura ratio values. APD was taken as the duration at 90 % repolarisation (APD90). When pacing frequency was increased from 0.25 Hz to 1 Hz, the rate constant of change of both APD90 and peak systolic [Ca2+]i were faster than when frequency was decreased. However the changes of [Ca2+]i were generally faster than those of APD90. For example, on increasing pacing frequency to 1 Hz, the change of peak systolic [Ca2+]i was approximately 5 fold faster than that of APD90 (APD, 0.056 ± 0.006 s-1; peak [Ca2+]i, 0.24 ± 0.05 s-1, n = 13, p<0.05). When pacing frequency was subsequently decreased to 0.25 Hz, the change in peak systolic [Ca2+]i was still faster than that of APD90 (APD, 0.029 ± 0.006 s-1; peak [Ca2+]i, 0.13 ± 0.04 s-1, n = 9, p=0.07). Diastolic [Ca2+]i changed approximately 10 fold faster than APD90 when pacing frequency was increased from 0.25 Hz to 1 Hz (APD, 0.056 ± 0.006 s-1; diastolic [Ca2+]i, 0.51 ± 0.09 s-1, n = 13, p<0.05). Upon a subsequent decrease of pacing frequency to 0.25 Hz, the rate constant of diastolic [Ca2+]i change was approximately 15 fold faster than that of APD90 (APD, 0.029 ± 0.006 s-1; diastolic [Ca2+]i, 0.45 ± 0.06 s-1, n = 9, p<0.05). The hysteresis of APD90 and peak and diastolic calcium (which both represent an absolute [Ca2+] in the cytoplasm), suggests that the slow change of APD90 is not dependent on a change of [Ca2+]i.

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