Expression and Function of Endothelial Ca 2+ -Activated K + Channels in Human Mesenteric Artery

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Abstract
—Ca 2+ -activated K + (K Ca ) channels have been suggested to play a role in the control of endothelial functions such as regulation of vascular tone and cell proliferation. We established a method for single-cell reverse transcriptase–polymerase chain reaction analysis in combination with the patch-clamp technique to characterize K Ca channel expression and function in single endothelial cells (ECs) within the endothelial monolayer of intact human mesenteric arteries (MAs) and in disease states. We tested whether endothelial K Ca channel expression and function are altered in MAs obtained from patients with colonic adenocarcinoma (CA) compared with those in MAs from non–cancer patients with inactive diverticulitis. Expression of the intermediate-conductance K Ca channel (hIK1) was detected in non–cancer and CA patients. In whole-cell patch-clamp measurements, only ECs expressing hIK1 exhibited corresponding K Ca currents, whereas respective K Ca currents were missing in hIK1-negative ECs. This heterogeneity of hIK1 expression patterns is indicative of a specialized subset of ECs within the endothelial monolayer. In CA patients, compared with non–cancer patients, a 2.5-fold increase in hIK1-expressing ECs per MA was observed ( P Ca current densities in hIK1-expressing ECs of both groups were similar. In addition to hIK1, expression of the large-conductance K Ca channel (hSlo) was detected in single ECs from CA patients. The increased K Ca channel expression in CA patients resulted in a 2.7-fold increase of bradykinin-induced endothelial hyperpolarization compared with controls ( P Ca channels might indicate an altered functional state of the endothelium in cancer patients and could play a role in tumor angiogenesis.