Cromakalim induces vasorelaxation in guinea-pig mesenteric vessels via hyperpolarization mediated by the opening of Ca-dependent K channels.
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 (greater than 10 microM) 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.
Nakao et al. (Tue,) studied this question.