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)