Activation of endothelial Ca2+ -dependent K+ -channels (KCa) of intermediate (IKCa) and small conductance (SKCa) is a prerequisite for endothelial hyperpolarization which subsequently hyperpolarizes and relaxes smooth muscle (EDHF-type dilation). The differential role of IKCa and SKCa in local and conducted dilations was assessed in cremaster arterioles of IKCa deficient (IK-/-) and wildtype mice (wt). Superfusion of ACh, SNP and adenosine (0.3-10mM) induced dilations in IK-/-, but ACh- responses were severely impaired compared to wt (1mM: 13 vs 41%; 10mM: 48 vs 66%) and resting tone enhanced (22 vs 31%). The remaining dilation was abrogated by additional blockade of SKCa with UCL1684 (100mM). Conducted responses were studied by focal agonist application and dilation assessed locally (0mm) and 1100mm upstream. The IKCa opener DCEBIO induced a conducted dilation in wt (0 mm: 31%; 1100 mm: 13%) but not in IK-/-. In response to ACh, local (62 vs 34%) and conducted responses (1100: 46 vs 19%) were diminished in IK-/-. Blockade of SKCa in wt did not affect local or conducted dilations upon ACh. We conclude that IKCa is of major importance in EDHF- type responses in arterioles. Sole activation of IKCa can initiate a conducted response, but its presence is not mandatory for the conduction of dilations along the arteriole.

Klinik für Innere Medizin - Nephrologie, Philipps-Universität, Marburg (R.K.,J.H.)