Characteristics of cromakalim‐induced relaxations in the smooth muscle cells of guinea‐pig mesenteric artery and vein

1 The effects of cromakalim (BRL 34915) on the smooth muscle cells of guinea‐pig mesenteric artery and vein were investigated with microelectrode and tension recording methods. 2 Cromakalim (> 10 μm) produced membrane hyperpolarization with an increase in ionic conductance. The hyperpolarization occurred to a greater extent and lasted longer in the vein than in the artery. 3 The hyperpolarization induced by cromakalim in mesenteric vein comprised two components, one of which was Mn sensitive. In mesenteric artery, the hyperpolarization was relatively insensitive to Mn. 4 From the current‐voltage relationship measured from arterial smooth muscle membranes, the reversal potential of cromakalim was estimated to be −80 mV. The cromakalim‐induced hyperpolarization was not modified in Na‐ or Cl‐deficient solution. 5 In both mesenteric artery and vein, cromakalim relaxed tissues precontracted with high K with (below 40 mm) or without (above 40 mm) hyperpolarization of the membrane. 6 In the mesenteric artery, action potentials evoked by electrical stimulation ceased before the generation of hyperpolarization. 7 Cromakalim produced a cross‐desensitization with nicorandil on the evoked membrane hyperpolarization in mesenteric artery. 8 It is concluded that the relaxing actions of cromakalim result from the hyperpolarization which follows the opening of Ca‐dependent K channels. The inhibition of a voltage‐dependent Ca current may also be involved in this inhibitory effect.