Nicorandil opens a calcium-dependent potassium channel in smooth muscle cells of the rat portal vein.
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)
Kajioka
S
S
Department of Second Oral Surgery, Faculty of Dentistry, Kyushu University, Fukuoka, Japan.
Oike
M
M
Kitamura
K
K
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*
D015221:Potassium Channels; D013757:Tetraethylammonium Compounds; D014665:Vasodilator Agents; D009536:Niacinamide; D020108:Nicorandil; D019789:Tetraethylammonium; D015761:4-Aminopyridine