Sd. Walker et al., Activation of endothelial cell IKCa with 1-ethyl-2-benzimidazolinone evokes smooth muscle hyperpolarization in rat isolated mesenteric artery, BR J PHARM, 134(7), 2001, pp. 1548-1554
1 In rat small mesenteric arteries contracted with phenylephrine, 1-ethyl-2
-benzimidazolinone (1-EBIO; 3-300 muM) evoked concentration-dependent relax
ation that, above 100 muM, was associated with smooth muscle hyperpolarizat
ion.
2 1-EBIO-evoked hyperpolarization (maximum 22.1+/-3.6 mV with 300 muM, n=4)
was endothelium-dependent and inhibited by charybdotoxin (ChTX 100 nM; n=4
) but not iberiotoxin (IbTX 100 nm; n=4).
3 In endothelium-intact arteries, smooth muscle relaxation to 1-EBIO was no
t altered by either of the potassium channel blockers ChTX (100 nM; n=7), o
r IbTX (100 nM; n=4), or raised extracellular K- (25 mM). Removal of the en
dothelium shifted the relaxation curve to the right but did not reduce the
maximum relaxation.
4 In freshly isolated mesenteric endothelial cells, 1-EBIO (600 muM) evoked
a ChTX-sensitive outward K-current. In contrast, 1-EBIO had no effect on s
mooth muscle cell conductance whereas NS 1619 (33 muM) stimulated an outwar
d current while having no effect on the endothelial cells.
5 These data show that with concentrations greater than 100 muM, 1-EBIO sel
ectively activates outward current in endothelial cells, which presumably u
nderlies the smooth muscle hyperpolarization and a component of the relaxat
ion. Sensitivity to block with charybdotoxin but not iberiotoxin indicates
this current is due to activation of IKCa. However, 1-EBIO can also relax t
he smooth muscle by an undefined mechanism, independent of any change in me
mbrane potential.