Endothelial K Ca 1.1 and K Ca 3.1 channels mediate rat intrarenal artery endothelium-derived hyperpolarization response

Endothelium-derived hyperpolarization (EDH)-mediated response plays an essential role in the control of kidney preglomerular circulation, but the identity of the K channels involved in this response is still controversial. We hypothesized that large- (K 1.1), intermediate- (K 3.1) and small (K 2.3) -conductance Ca -activated K (K ) channels are expressed in the endothelium of the preglomerular circulation and participate in the EDH-mediated response. We study the functional expression of different K channels in non-cultured, freshly isolated native endothelial cells (ECs) of rat intrarenal arteries using immunofluorescence and the patch-clamp technique. We correlate this with vasorelaxant responses ex vivo using wire myography. Immunofluorescence revealed the expression of K 1.1, K 3.1 and K 2.3 channels in ECs. Under voltage-clamp conditions, acetylcholine induced a marked increase in the outward currents in these cells, sensitive to the blockade of K 1.1, K 3.1 and K 2.3 channels respectively. Isometric myography experiments, under conditions of endothelial nitric oxide synthase and cyclooxygenase inhibition, showed that blockade either of K 1.1 or K 3.1 channels was able to reduce the endothelium-derived vasorelaxation of isolated interlobar arteries, while their combined blockade completely abolished it. In contrast, blockade of K 2.3 channels did not reduce this vasorelaxant response, despite being functionally expressed in the endothelial cells. This study shows that K 1.1 and K 3.1 channels are functionally expressed at the renal vascular endothelium and play a central role in the EDH-mediated relaxation of kidney preglomerular arteries, which is important in the control of renal blood flow and glomerular filtration rate.