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 mumol/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 mumol/l) caused a similar channel activation. GDP-beta-S (100 mumol/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.