EFFECTS OF RELAXIN ON RAT ATRIAL MYOCYTES .1. INHIBITION OF I-TO VIA PKA-DEPENDENT PHOSPHORYLATION

The peptide hormone relaxin has direct, positive inotropic and chronot ropic effects on rat hearts in vivo and in vitro. Relaxin's effects on the electrophysiological properties of single quiescent atrial cells from normal rats were investigated with a whole cell patch clamp. Rela xin had a significant inhibitory effect on outward potassium currents. The outward potassium current consisted of a transient component (I-t o) and a sustained component (I-S). The addition of 100 ng/ml of relax in inhibited the peak I-to in a voltage-dependent manner (74% inhibiti on at a membrane potential of -10 mV to 30% inhibition at +70 mV). The time to reach peak I-to and the apparent time constant of inactivatio n of I-to were increased by relaxin. Dialysis with the protein kinase A inhibitor 5-24 amide (2 mu M) prevented relaxin's effects, suggestin g an obligatory role for this kinase in the relaxin-dependent regulati on of the potassium current.