Effects of atrionatriuretic factor on Ca2+ current and Cai-independent transient outward K+ current in human atrial...

The effect of 10 nM atrial natriuretic peptide (ANF) on macroscopic L-type calcium current, ICa, and calcium-independent outward potassium current, Ilo, were studied in myocytes isolated from human atrial trabeculae using the whole-cell-recording patch-clamp technique. When cells were dialysed with pipette media containing 0.2 mM GTP, ANF reduced ICa by 37.81% +/- 5.4% at +20 mV and Ilo by 21.72% +/- 3.68% at +60 mV in a reversible manner. When ICa was increased by beta-adrenoreceptor stimulation (0.1 microM isoproterenol) or by the phosphodiesterase inhibitor isobutylmethylxanthine (10 microM) ANF reduced ICa by 24.99 +/- 3.4% and by 39.9 +/- 6.3% respectively. In cells dialysed with GTP-free pipette media, ANF increased ICa markedly (39.8% +/- 7%) and reversibly, whereas it still depressed Ilo (18.92% +/- 2%). Addition of 0.2 mM GTP[gamma S] to the pipette solution in the absence of GTP increased ICa, decreased Ilo and suppressed the effect of ANF on both ICa and Ilo. It is suggested that activation of the ANF receptor in human atrial cells reduces ICa via guanylate-cyclase-dependent cGMP production, increases ICa via Gs protein activation and decreases Ilo via Gi protein activation.