We have shown I_Ks to have reduced density and altered kinetics in epicardial border zone cells (IZs) of the 5-day infarcted canine heart(10). -adrenergic stimulation with isoproterenol (ISO) increases IKs in normal cells (NZs). In this study we determined the effects of 1mM ISO on I_Ks in IZs and NZs using voltage clamp with an external solution to isolate IKs from contaminating currents. 10mM Azimilide-sensitive (AZ) currents with ISO were used to compare responsiveness of I_Ks to ISO in the two cell groups. In 67% of IZs (Grp I, n=26), I_Ks tail density was reduced vs NZs(n=24, P<0.05). ISO-stimulated AZ tail currents were 1.72±0.2 fold increased in NZs and 2.2±0.3 fold in IZs (P>0.05). Importantly, in 33% of IZs(n=13, Grp II), native currents showed no tail currents but ISO-stimulated AZ currents were voltage-dependent, fast activating and large in amplitude vs Grp I IZ value, similar to "lone" KCNQ1 currents. Using short clamp pulses, we also determined that IZs with little or no transient outward currents have increased sustained currents sensitive to TEA and no change in C9356-sensitive currents. Conclusions: In some IZs where I_Ks is downregulated, ISO affected I_Ks as it affected I_Ks in NZs. In others, "lone" KCNQ1-type currents, which are sensitive to adrenergic stimulation, exist and are consistent with our findings of an increased KCNQ1/KCNE1 mRNA ratio (10) . Accompanying altered I_Ks currents in IZs is an enhanced TEA-sensitive current and normal C9356-sensitive currents.