THYROID STATUS AND DIABETES MODULATE REGIONAL DIFFERENCES IN POTASSIUM CURRENTS IN RAT VENTRICLE

1. The rate dependence and recovery kinetics of the Ca2+-independent t ransient (I-t) and steady-state or 'pedestal' (I-ss) outward potassium (K+) currents were studied in single myocytes isolated from epicardia l and endocardial res ions of rat left ventricles. The whole-cell, suc tion microelectrode method was used to measure baseline (fully reactiv ated) I-t, as well as its rate-dependent attenuation. Results from a g roup of control animals were compared with data from three other group s having an experimentally altered hormonal status. 2. I-t was signifi cantly smaller in endocardial cells than in epicardial cells, in part due to a very large difference in the recovery kinetics of this curren t in endocardial cells. This was reflected in a pronounced rate-depend ent prolongation of endocardial action potentials. In contrast, the no n-inactivating 'pedestal' current, I-ss, was very similar in magnitude and showed comparable rate dependence in cells from both epicardium a nd endocardium. 3. Changing the thyroid status had selective, differen tial actions on the amplitude and rate dependence of I-t in epicardial and endocardial cells. Under hypothyroid conditions there was a more pronounced reduction of baseline I-t in epicardial than in endocardial cells. Moreover, a slowing of the recovery kinetics in epicardial cel ls resulted in an enhanced attenuation of this current at high rates. Changing thyroid status had no effect on the magnitude or rate depende nce of I-ss in cells from either region of the left ventricle. 4. Foll owing establishment of hyperthyroid conditions, there was no significa nt change in I-t magnitude at baseline. However, when compared with co ntrol data, the recovery of I-t was considerably faster in endocardial cells, and marginally faster in epicardial cells. 5. Streptozotocin-i nduced diabetic conditions resulted in a much greater attenuation of I -t in epicardial cells than in endocardial cells. Epicardial action po tentials in these conditions showed prominent rate-dependent prolongat ion. I-ss was reduced to a similar extent in cells from these two regi ons. 6. Our findings demonstrate that altered hormonal status can sele ctively change the amplitude and kinetics of I-t in the epi- and endoc ardium of rat left ventricle. These changes can reduce the epicardial- endocardial gradients in the magnitude and recovery kinetics of I-t an d hence diminish the intrinsic differences in both action potential du ration and refractoriness.