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Am J Physiol Heart Circ Physiol 278: H2028-H2038, 2000;
0363-6135/00 $5.00
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Vol. 278, Issue 6, H2028-H2038, June 2000

Sulfonylurea receptor ligands modulate stretch-induced ANF secretion in rat atrial myocyte culture

Jin-Hua Jiao1, Philippe Baumann2, Anne Baron2, Angela Roatti2, Richard A. Pence1, and Alex J. Baertschi1,2

1 Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, Virginia 22903; and 2 Department of Physiology, University of Geneva, 1211 Geneva, Switzerland

Stretch-induced atrial natriuretic factor (ANF) secretion was studied in cultures of neonate atrial appendage myocytes. Stretch, applied for 40 min by hypotonic swelling, increased the mean area of 44 individually imaged myocytes by 4.8-8.8% (P < 0.0001) at 6 min and by 2.3-6.2% (P < 0.05) at 35 min. Stretch increased immunoreactive ANF release by 42% (P < 0.05) from a baseline of 315 pg/ml. The ATP-sensitive K+ (KATP)-channel blocker tolbutamide (100 µmol/l) increased the stretch-stimulated release to 84% (P < 0.01) over baseline, whereas lower concentrations (1, 10, and 30 µmol/l) had no stimulatory effect. The KATP-channel opener diazoxide (0.1, 1, 10, 30, and 100 µmol/l) inhibited stretch- plus tolbutamide-stimulated ANF release in a concentration-dependent manner, with IC50 = 2.2 µmol/l, although 100 µmol/l diazoxide did not reduce the increase in mean cell area. The stretch-stimulated KATP current, monitored in 82 whole cell recordings with sulfonylurea receptor (SUR) ligands, was inversely correlated with the stretch-induced ANF release (r2 = 0.79, P < 0.0001). In the absence of stretch, the KATP current had no relationship with baseline ANF release, and baseline ANF release was not affected by the KATP-channel modulators. The results show that SUR ligands that open KATP channels inhibit stretch-induced ANF release in atrial myocytes, in correlation with the stretch-activated KATP current. The subcellular site of action of the SUR ligands---plasmalemma or intracellular organelles---remains to be determined.

atrial natriuretic factor; atrial natriuretic factor regulation; diazoxide; adenosine 5'-triphosphate-sensitive potassium channels; tolbutamide


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