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1 Department of Pharmacology, Columbia University, NY, NY, USA
* To whom correspondence should be addressed. E-mail: pab4{at}columbia.edu.
Objective: Action potentials(APs) of the epicardial border zone(EBZ) cells from the 5 day infarcted heart continue to be altered by the 14th day post occlusion, namely they shortened. However, by 2 months, EBZ APs appear "normal", yet conduction of wavefronts remains abnormal. We hypothesize that the changes in transmembrane APs are due to a change in the distribution of ion channels either in density or function. Thus here we focused on the changes in Ca2+ and K currents in cells isolated from the 14 day(IZ14d) and 2 month(IZ2M) EBZ and compared them to those occurring in cells from the same hearts but remote(Rem) from the EBZ.
Methods: Whole cell voltage-clamp techniques were used to measure and compare Ca2+ and K currents in cells from the different groups.
Results: Ca2+ current densities remain reduced in cells of the 14d and 2mon infarcted heart and the kinetic changes previously identified in the 5 day heart begin to, but do not recover to NZ values. Importantly, I,CaL in both the EBZ and Rem regions still show a slowed recovery from inactivation. Furthermore, during the remodeling process, there is an increased expression of T type Ca2+ currents but only regionally, and only within a specific time window post MI. Regional heterogeneity in 
adrenergic responsiveness of ICaL exists between EBZ and remote cells of the 14d hearts, but this regional heterogeneity is gone in the healed infarcted heart. In IZM14d Ito begins to reemerge and is accompanied by an upregulated TEA-sensitive outward current. By 2months post occlusion, Ito/Isus currents have completed the reverse remodeling process.
Conclusions: During the healing process post MI, canine epicardial cells downregulate the fast Ito but compensate by upregulating a K current that in normal cells is minimally functional. For recovering L type Ca2+ currents of the 14d and 2month EBZ cells, voltage-dependent processes appear to be reset, such that ICaL "window" current occurs at hyperpolarized potentials. Thus dynamic changes in both Ca2+ and K currents to the altered AP observed in 14d fibers and may account for return of APs of 2mon EBZ fibers.
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