ATRIAL-NATRIURETIC-FACTOR AND ISOSORBIDE DINITRATE MODULATE THE GATING OF ATP-SENSITIVE K+ CHANNELS IN CULTURED VASCULAR SMOOTH-MUSCLE CELLS

The effects of atrial natriuretic factor (ANF) and isosorbide dinitrate (ISDN), activators of particulate and soluble guanylate cyclase, respectively, on K+ currents were investigated in patch-clamp recordings of smooth muscle cells cultured from rat thoracic aorta. In the cell-attached patch configuration, ANF enhanced Ca2+-activated K+ (K-Ca) channel activities as reported previously. When K-Ca channels were blocked with 1 mmol/L tetraethylammonium or 10(-7) mol/L charybdotoxin, ANF and ISDN applied to the bathing solution activated ATP-sensitive K+ (K-ATP) channels without altering channel conductance. Pretreatment with methylene blue, a guanylate cyclase inhibitor, abolished the effects of ISDN on K-ATP channels, whereas 8-bromo-cGMP activated these channels, suggesting that the effects of ISDN on K-ATP channels were mediated by cGMP. Our results suggest that vasorelaxant agents that increase intracellular cGMP concentrations modulate the gating of two major potassium channels, ATP sensitive and Ca2+ activated, that might play an important role in controlling vascular tone by changing the membrane potential. (Circ Res. 1994;74:471-476.)