Modulation of the delayed rectifier K+ current by isoprenaline in bull‐frog atrial myocytes.

Abstract

1. The effects of isoprenaline (ISO) on the calcium current (ICa) and delayed rectifier K+ current (IK) were examined using a tight‐seal whole‐cell voltage‐clamp technique in single cells from bull‐frog atrium to examine the ionic mechanism(s) of catecholamine‐induced action potential shape changes. 2. The effects of ISO on the action potential were dose‐dependent. Very low doses (5 x 10(‐9) M) prolonged the action potential. Higher doses (10(‐6) M) of ISO increased the plateau height, but shortened the action potential by accelerating the early repolarization phase. 3. ISO increased IK and ICa in a dose‐dependent fashion. Both of these effects were blocked by a beta‐receptor antagonist, propranolol (3 x 10(‐7) M). In contrast IK1, the inwardly rectifying K+ current, was not changed significantly by ISO. 4. The ISO‐induced increase in IK was observed in the presence of CdCl2 (3 x 10(‐4) M), indicating that this effect is not due to a Ca2(+)‐activated potassium current. 5. The reversal potential of IK in normal Ringer solution (‐83 +/‐ 2 mV) was not significantly changed by ISO. Thus, stimulation of the Na(+)‐K+ pump and a consequent hyperpolarizing shift in EK are not responsible for the increase in IK. 6. In the presence of ISO (10(‐6) M) the steady‐state activation curve (n infinity) for IK was consistently shifted to more negative values (by approximately 10 mV). The activation and deactivation kinetics of IK were also changed by ISO: activation was accelerated, deactivation was slowed. These ISO‐induced changes in IK result in an increase in IK at voltages corresponding to the plateau of the action potential. 7. ISO (10(‐6) M) increased ICa dramatically, approximately 6‐fold at 0 mV. At the same time, the time constant of ICa inactivation decreased significantly (34 +/‐ 4 ms control; 23 +/‐ 4 ms ISO). 8. These results confirm that low doses of sympathetic agonists acting via beta‐receptors increase ICa. Relatively high doses of beta‐receptor agonists increase both ICa and IK, but these two effects appear to be generated by different biophysical mechanisms. 9. These dose‐dependent changes in ICa and IK can explain the observed ISO‐induced changes in action potential shape. At doses of approximately 10(‐8) M ICa is increased, resulting in a more depolarized plateau and small lengthening of the action potential.(ABSTRACT TRUNCATED AT 400 WORDS)