ENHANCED NA-CA2+ EXCHANGE IN THE INFARCTED HEART - IMPLICATIONS FOR EXCITATION-CONTRACTION COUPLING()

Cellular Ca2+ regulation is abnormal in diseased hearts. We designed t his study to assess the role of the Na+-Ca2+ exchanger in excitation-c ontraction coupling in surviving myocardium of the infarcted heart. We measured cellular contractions and whole-cell currents in single left ventricular myocytes isolated from the hearts of rabbits with healed myocardial infarction (MI). Eight weeks after MI, rabbits had left ven tricular dysfunction without overt heart failure. Myocytes isolated fr om regions adjacent to the infarcted zone were significantly longer th an cells from control hearts. At low stimulation rates (0.5 Hz), the a mplitude of field-stimulated contractions was increased (11.6+/-0.5% v ersus 10.2+/-0.6% resting cell length), whereas the time to peak short ening and action potential duration were prolonged in the MI cells. Wh en stimulation frequency was increased to 2.0 Hz, cellular shortening did not change or decreased in myocytes from infarcted hearts, whereas control cells had a positive shortening-interval relationship. Cells from infarcted hearts had a significantly decreased (31%) L-type Ca2current (I-Ca) density but no change in the current-voltage relationsh ip or the kinetics of I-Ca inactivation. Maximal Na+-Ca2+ exchange cur rent density was significantly increased (32%) in the cells from infar cted hearts. Sarcoplasmic reticulum (SR) Ca2+ content during a stable train of contractions, as estimated from caffeine-induced inward curre nts, was slightly increased (P=NS) in the MI myocytes. To determine wh ether Na+-Ca2+ exchange influenced SR Ca2+ content, cells were clamped at potentials between -70 and +90 mV for 400 ms. The amplitude of the contraction during a subsequent clamp step to +10 mV was then measure d as an index of SR loading that occurred during the preceding clamp s tep. Steps to positive potentials produced greater augmentation of the subsequent contraction in MI than in control myocytes. In myocytes fr om the infarcted heart, increased activity of the Na+-Ca2+ exchanger m ay promote Ca2+ entry or decrease Ca2+ extrusion. This relative augmen tation of inward Ca2+ flux by the exchanger may enhance SR Ca2+ loadin g and thus support contractility that would otherwise be impaired as a result of decreased Ca2+ current. However, Ca2+ influx by the exchang er may contribute to the prolongation of contractions in myocytes from infarcted hearts.