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

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)