MODULATION OF THE DELAYED RECTIFIER POTASSIUM CURRENT IN FROG CARDIOMYOCYTES BY fl-ADRENERGIC AGONISTS AND MAGNESIUM BY ISABELLE

1. The regulation of'K and ICa were studied in single cells isolated from bull-frog atrium using the whole-cell configuration of the patch clamp and a perfused patch pipette. 2. IK was increased approximately 50-100% and ICa was increased approximately 6-10 times by 1 /LM-isoprenaline, 5 jtM-forskolin, or internal perfusion with 30 ,UMcyclic AMP. The effects of cyclic AMP and isoprenaline were not additive. The shape of the concentration-response curves and the EC50 values for the effects of cyclic AMP on ICa and on IK were very similar (2-3 ,UM for IK and 1-7 /UM for ICa). 3. Elevation of intracellular cyclic AMP had a similar effect on IK regardless of whether ICa was blocked with Cdd2+ or not. Increasing Ica with dihydropyridine Caa2+ channel agonists had no effect on 'K amplitude. 4. Isoprenaline or cyclic AMP caused an increase in the fully-activated IK and also shifted the activation curves to more negative potentials in most cells. The shift in the activation curve was reversible and was also observed when ICa was blocked with Cd2+. The rate of activation ofIK was increased and the rate of deactivation ofIK was slowed by isoprenaline. 5. After breaking the membrane patch and initiating whole-cell recording, IK ran down with time in about 50°% of the cells examined when the intracellular solution contained 1 mM [Mg2+]. In contrast, when the solution contained 0 3 mm [Mg2+], rundown was almost never observed. Internal perfusion with increasing concentrations of [Mg2+] caused reversible decreases in the maximum amplitude of1K and shifted the IK activation curve slightly to more negative potentials, but had negligible effects upon the shape or the curvature of the fully activated current-voltage relationship.