title: Nicorandil opens a calcium-dependent potassium channel in smooth muscle cells of the rat portal vein.
abstract: The actions of nicorandil on ionic currents recorded from smooth muscle cells of the rat portal vein were investigated using patch-clamp technique. In the whole-cell voltage clamp experiments, nicorandil (greater than 30 microM) produced an outward current in a concentration-dependent manner. The reversal potential was -80 mV. The nicorandil-induced outward current was suppressed in the nominally Ca-free (2.5 mM Mn-containing) solution. Tetraethylammonium (greater than 1 mM) and 4-aminopyridine (greater than 1 mM) inhibited the nicorandil-induced outward current. Recordings of single K-channels showed that there were two types of K currents with different conductance (132 pS and 10 pS) in the smooth muscle cell membrane. Both channels were sensitive to intracellular Ca concentration. The 10-pS K-channel but not the 132-pS K-channel was activated by lowering the ATP concentration inside of the membrane. Low concentrations of tetraethylammonium (less than 1 mM) completely inhibited the 132-pS K-channel, but had no effect on the 10-pS K-channel. On the other hand, 4-aminopyridine (10 mM) inhibited the 10-pS K-channel but not 132-pS K-channel. Nicorandil (500 microM) applied to outside of the membrane increased the mean open-time and number of appearances but reduced slow component of the mean closed time of the 10-pS K-channel current, without affecting their amplitudes. Nicorandil (less than 500 microM) did not modify the 132-pS K-channel. From above results we concluded that nicorandil activates the Ca-dependent and ATP-sensitive K-channel in smooth muscle cells of the rat portal vein.(ABSTRACT TRUNCATED AT 250 WORDS)
authors: Department of Second Oral Surgery, Faculty of Dentistry, Kyushu University, Fukuoka, Japan.
authors: S
authors: S
authors: Kajioka
authors: M
authors: M
authors: Oike
authors: K
authors: K
authors: Kitamura
mesh_terms: D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D004553:Electric Conductivity / Q000187:drug effects; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D020108:Nicorandil; D011169:Portal Vein; D015221:Potassium Channels / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D015221:Potassium Channels; D013757:Tetraethylammonium Compounds; D014665:Vasodilator Agents; D009536:Niacinamide; D020108:Nicorandil; D019789:Tetraethylammonium; D015761:4-Aminopyridine