I-NaCa contributes to electrical heterogeneity within the canine ventricle

This study examines the amplitude of sodium-calcium exchange current (I-NaC a) in epicardial, midmyocardial, and endocardial canine ventricular myocyte s. Whole cell currents were recorded at 37 degrees C using standard or perf orated-patch voltage-clamp techniques in the absence of potassium, calcium- activated chloride, and sodium-pump currents. INaCa was triggered by releas e of calcium from the sarcoplasmic reticulum or by rapid removal of externa l sodium. INaCa was large in midmyocardial myocytes and significantly small er in endocardial myocytes, regardless of the method used to activate I-NaC a. I-NaCa at -80 mV was -0.316 +/- 0.013, -0.293 +/- 0.016, and -0.210 +/- 0.007 pC/pF, respectively, in midmyocardial, epicardial, and endocardial my ocytes when activated by the calcium transient. When triggered by sodium re moval, peak I-NaCa was 0.74 +/- 0.04, 0.57 +/- 0.04, and 0.50 +/- 0.03 pA/p F, respectively, in midmyocardial, epicardial, and endocardial myocytes. Ep icardial I-NaCa was smaller than midmyocardial I-NaCa when activated by rem oval of external sodium but was comparable to epicardial and midmyocardial I-NaCa when activated by the normal calcium transient, implying possible tr ansmural differences in excitation-contraction coupling. Our results sugges t that I-NaCa differences contribute to transmural electrical heterogeneity under normal and pathological states. A large midmyocardial I-NaCa may con tribute to the prolonged action potential of these cells as well as to the development of triggered activity under calcium-loading conditions.