SINGLE CARDIAC OUTWARDLY RECTIFYING K+ CHANNELS MODULATED BY PROTEIN KINASE-A AND A G-PROTEIN

Elementary K+ currents were recorded at 19-degrees-C in cell-attached and in inside-out patches excised from neonatal rat heart myocytes. An outwardly rectifying K+ channel which prevented Na+ ions from permeating could be detected in about 10% of the patches attaining (at 5 mmol/l external K+ and between -20 mV and +20 mV) a unitary conductance of 66 +/- 3.9 pS. K+(outw.-rect.) channels have one open and at least two closed states. Open probability and tau-open rose steeply on shifting the membrane potential in the positive direction, thereby tending to saturate. Open probability (at -7 mV) was as low as 3 +/- 1% but increased several-fold on exposing the cytoplasmic surface to Mg-ATP (100-mu-mol/l) without a concomitant change of tau-open. No channel activation occurred in response to ATP in the absence of cytoplasmic Mg++. The cytoplasmic administration of the catalytic subunit of protein kinase A (120-150-mu/ml) or GTP-gamma-S (100-mu-mol/l) caused a similar channel activation. GDP-beta-S (100-mu-mol/l) was also tested and found to be ineffective in this respect. This suggests that cardiac K+(outw.-rect.) channels are metabolically modulated by both cAMP-dependent phosphorylation and a G-protein.