Nicorandil opens a calcium-dependent potassium channel in smooth muscle cells of the rat portal vein

S. Kajioka, M. Oike, K. Kitamura

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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 (>30 μM) 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 (>1 mM) and 4-aminopyridine (>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 tetraetylammonium (<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 μM) 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 (<500 μM) 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. Activation of this channel may cause a hyperpolarization of the membrane.

Original languageEnglish
Pages (from-to)905-913
Number of pages9
JournalJournal of Pharmacology and Experimental Therapeutics
Volume254
Issue number3
Publication statusPublished - Oct 17 1990

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Pharmacology

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