ALTERATIONS OF NA- A POSSIBLE IONIC MECHANISM FOR REDUCED EXCITABILITY AND POSTREPOLARIZATION REFRACTORINESS( CURRENTS IN MYOCYTES FROM EPICARDIAL BORDER ZONE OF THE INFARCTED HEART )

Previously, we have shown abnormalities in (V) over bar (max) and in t he recovery of (V) over bar (max) in myocytes dispersed from the epica rdial border zone (EBZ) of the 5-day infarcted canine heart (myocytes from the EBZ [IZs]). Thus, we sought to determine the characteristics of the whole-cell Na+ current I-Na) in IZs and compare them with the I -Na of cells from noninfarcted hearts (myocytes from noninfarcted epic ardium [NZs]). I-Na was recorded using patch-clamp techniques under co nditions that eliminated contaminating currents and con trolled I-Na f or measurement (19 degrees C, 5 mmol/L [Na+](0)). Peak I-Na density (a t -25 mV) was significantly reduced in IZs (4.9+/-0.44 pA/pF, n=36) ve rsus NZs (12.8+/-0.55 pA/pF, n=54; P<.001), yet the half-maximal activ ation voltage (V-0.5), time course of decay, and time to peak I-Na wer e no different. However, in IZs, V-0.5 of the availability curve (I/I- max curve) was shifted significantly in the hyperpolarizing direction (-80.2+/-0.48 mV in NZs [n=45] versus -83.9+/-0.59 mV in IZs [n=27], P <.01). Inactivation of I-Na directly from a depolarized prepotential ( -60 mV) was significantly accelerated in IZs versus NZs (fast and slow time constants [tau(1) and tau(2) respectively] were as follows: NZs [n=28], tau(1)=71.5+/-5.6 ms and tau(2)=243.7+/-17.1 ms; IZs [n=21], t au(1)=36.3+/-2.4 ms and tau(2)=153+/-11.3 ms; P<.001). Recovery of I-N a from inactivation was dependent on the holding potential (V-H) in bo th cell types but was significantly slower in IZs. At V-H= -90 mV, I-N a recovery had a lag in 18 (82%) of 22 IZs (with a 17.6+/-1.5-ms lag) versus 2 (9%) of 22 NZs (with 5.9- and 8.7-ms lags); at V-H=-100 mV, t au(1)=60.9+/-2.6 ms and tau(2)=352.8+/-28.1 ms in NZs (n=41) versus ta u(2)=76.3+/-4.8 ms and tau(2)=464.3+/-47.2 ms in IZs (n=26) (P<.002 an d P<.03, respectively); at V-H=-110 mV, tau(1)=33.4+/-1.8 ms and tau(2 )=293.5+/-33.6 ms in NZs (n=21) versus tau(1)=44.3+/-2.9 ms and tau(2) =388.4+/-38 ms in IZs (n=18) (P<.002 and P<.07, respectively). In sum, I-Na is reduced, and its kinetics are altered in IZs. These changes m ay underlie the altered excitability and postrepolarization refractori ness of the ventricular fibers of the EBZ, thus contributing to reentr ant arrhythmias in the infarcted heart.