© 2000 American Heart Association, Inc.
Cellular Biology |
Expression and Function of Endothelial Ca2+-Activated K+ Channels in Human Mesenteric Artery
A Single-Cell Reverse Transcriptase–Polymerase Chain Reaction and Electrophysiological Study In Situ
From the Departments of Nephrology (R.K., C.D., M.K., J.H.), Clinical Pharmacology (M.P.), and Surgery (N.R.), Benjamin Franklin Medical Center, Freie Universität, Berlin, Germany.
Abstract—Ca2+-activated K+ (KCa) 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 KCa 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 KCa 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 KCa channel (hIK1) was detected in non–cancer and CA patients. In whole-cell patch-clamp measurements, only ECs expressing hIK1 exhibited corresponding KCa currents, whereas respective KCa 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<0.05). However, KCa current densities in hIK1-expressing ECs of both groups were similar. In addition to hIK1, expression of the large-conductance KCa channel (hSlo) was detected in single ECs from CA patients. The increased KCa channel expression in CA patients resulted in a 2.7-fold increase of bradykinin-induced endothelial hyperpolarization compared with controls (P<0.05). This increased expression and function of KCa channels might indicate an altered functional state of the endothelium in cancer patients and could play a role in tumor angiogenesis.
Key Words: single-cell RT-PCR • endothelium • Ca2+-activated K+ channels • colonic cancer
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