EFFECT OF DURATION OF DEPOLARIZATION ON CONTRACTION OF NORMAL AND HYPERTROPHIED FELINE VENTRICULAR MYOCYTES

Objective: 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. Methods: Left ventricular hypert rophy 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 d epolarisation. Results: Action potential duration measured at 50% repo larisation (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 [hypertr ophied myocytes 609(54) ms, control myocytes 406(13) ms]. The absolute magnitude of shortening normalised to percent diastolic cell length w as also significantly reduced in hypertrophied myocytes [7.8(0.8)% dia stolic cell length] compared to control myocytes [12.2(0.6)% diastolic cell length] and the duration of contraction time to 50% relengthenin g was prolonged [406(13) ms v 609(54) ms]. When the duration of depola risation was controlled with voltage clamp techniques, steady state co ntractions at +10 mV increased in magnitude in bath control and hypert rophied myocytes as the duration of depolarization was lengthened. At all durations tested (100-1000 ms), contractions were significantly lo nger in duration in hypertrophied myocytes. Changing the duration of d epolarisation 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 contracti on. Steady state contractions initiated from -70 mV (sodium current ac tivated) were larger in both control and hypertrophied myocytes than c ontractions elicited from -40 mV (sodium current inactivated), and the effect of depolarisation duration on contractile duration was the sam e. Conclusions: Changes in sarcolemmal properties which produce a leng thening of the action potential duration in hypertrophy are not primar ily responsible for the prolongation of contractile duration. However, there is a portion of contraction which becomes sensitive to the dura tion of depolarisation in hypertrophied myocytes.