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 Ca(2+)-activated K+ (KCa) channel activities as reported previously. When KCa 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+ (KATP) channels without altering channel conductance. Pretreatment with methylene blue, a guanylate cyclase inhibitor, abolished the effects of ISDN on KATP channels, whereas 8-bromo-cGMP activated these channels, suggesting that the effects of ISDN on KATP 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.
Kubo
M
M
Department of Pediatrics, University of Tokushima, Japan.
Nakaya
Y
Y
Matsuoka
S
S
Saito
K
K
Kuroda
Y
Y
D000255:Adenosine Triphosphate / Q000502:physiology*; D000818:Animals; D001013:Aorta, Thoracic; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000494:pharmacology; D015640:Ion Channel Gating / Q000187:drug effects*; D007548:Isosorbide Dinitrate / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D051381:Rats
D015221:Potassium Channels; C016276:8-bromocyclic GMP; D009320:Atrial Natriuretic Factor; D000255:Adenosine Triphosphate; D006152:Cyclic GMP; D007548:Isosorbide Dinitrate