HYPERTHYROIDISM SELECTIVELY MODIFIED A TRANSIENT POTASSIUM CURRENT IN RABBIT VENTRICULAR AND ATRIAL MYOCYTES

1. Transient outward potassium currents (It) were compared in single cardiac myocytes obtained from normal and hyperthyroid rabbits. Currents were recorded using the suction electrode whole-cell voltage clamp technique. 2. In ventricular myocytes from hyperthyroid animals (at 22-degrees-C and a stimulation rate of 0.2 Hz), I(t) was 4- to 5-fold larger than in normal myocytes, in a potential range of -20 to +60 mV. As in normal myocytes, I(t) in hyperthyroid myocytes was calcium insensitive, and was more than 90 % suppressed by 2 mm 4-aminopyridine. 3. The increase in I(t) was observed over a wide range of stimulation rates, even at rates sufficiently slow to enable complete reactivation of the I(t) channels. However, there was a major change in the rate dependence of I(t) in hyperthyroid myocytes, with significant I(t) current still present at rates (e.g. 1-2 Hz) at which it is normally completely suppressed. 4. The augmentation of I(t) in the hyperthyroid myocytes could not be accounted for by changes in the voltage dependence or the kinetics of channel activation or inactivation. There was no change in the reversal potential of I(t), implying no change in the selectivity of the channel. 5. Single-channel activity was recorded using the cell-attached mode of recording. In myocytes from hyperthyroid rabbit we observed the following: (a) active patches (often containing two channels) were obtained more frequently in comparison to control; (b) the unitary conductance of the channel was the same; (c) single-channel openings persisted at high stimulation rates. 6. In contrast to hyperthyroid ventricular cells, I(t) in atrial cells from the same hearts was not substantially changed. 7. The rate dependence of I(t) in atrial cells was also unaffected by hyperthyroidism, in contrast to the large changes observed in ventricular cells. Thus, in atrial cells from hyperthyroid hearts the current was totally suppressed at rates of 1-2 Hz, as in euthyroid conditions. 8. Single-channel recordings in the cell-attached mode showed a unitary conductance similar to that found in normal atrial cells. Channel activity was suppressed at 2 Hz, in contrast to hyperthyroid ventricular cells. 9. In conclusion, I(t) is drastically changed in hyperthyroid rabbit ventricle cells. The changes are in the magnitude of the macroscopic current and its rate dependence. Since the unitary conductance is unchanged (and the peak open probabilities are normally high at positive membrane potentials) the number of active channels in the membrane must be increased. In atrial cells from the same hyperthyroid hearts no changes are apparent. These results are discussed in terms of the functional implications for action potential configuration, and in terms of the changes which occur in myosin isozyme pattern changes in the two cardiac tissues. This is related to the issue of long-term cardiac electrical and mechanical adaptation.