Effect of duration of depolarisation on contraction of normal and hypertrophied feline ventricular myocytes.

Abstract

The aim was to test the hypothesis that the prolongation of action potential duration in hypertrophied feline myocytes causes the contractions to be of long duration. Left ventricular hypertrophy was induced by slow progressive pressure overload after banding the ascending aorta of young cats. Single myocytes were enzymatically dissociated for whole cell patch clamp studies. Cell shortenings were induced by stimulated action potentials (in current clamp mode) and by step depolarisations using voltage clamp to control the duration of depolarisation. Action potential duration measured at 50% repolarisation (0.5 Hz) was significantly longer in hypertrophied myocytes, at 688(SEM 43) ms, n = 25, v 396(17) ms, n = 22, in control myocytes (p < 0.01). The associated contractions in hypertrophied myocytes had significantly longer durations measured at 50% relengthening [hypertrophied myocytes 609(54) ms, control myocytes 406(13) ms]. The absolute magnitude of shortening normalised to percent diastolic cell length was also significantly reduced in hypertrophied myocytes [7.8(0.8)% diastolic cell length] compared to control myocytes [12.2(0.6)% diastolic cell length] and the duration of contraction time to 50% relengthening was prolonged [406(13) ms v 609(54) ms]. When the duration of depolarisation was controlled with voltage clamp techniques, steady state contractions at +10 mV increased in magnitude in both control and hypertrophied myocytes as the duration of depolarization was lengthened. At all durations tested (100-1000 ms), contractions were significantly longer in duration in hypertrophied myocytes. Changing the duration of depolarisation had no significant effect on the duration of contraction in control myocytes. In hypertrophied myocytes, however, prolongation of depolarisation (500-1000 ms) significantly prolonged the contraction. Steady state contractions initiated from -70 mV (sodium current activated) were larger in both control and hypertrophied myocytes than contractions elicited from -40 mV (sodium current inactivated), and the effect of depolarisation duration on contractile duration was the same. Changes in sarcolemmal properties which produce a lengthening of the action potential duration in hypertrophy are not primarily responsible for the prolongation of contractile duration. However, there is a portion of contraction which becomes sensitive to the duration of depolarisation in hypertrophied myocytes.