Increased Expression of Ca2+ -Sensitive K+ Channels in Aorta of Hypertensive Rats

• Published in: Hypertension (Dallas, Tex. 1979) Tex. 1979), 1997-12, Vol.30 (6), p.1403-1409
• Main Authors: Liu, Yanping, Pleyte, Kay, Knaus, Hans-Guenther, Rusch, Nancy J
• Format: Article
• Language: English
• Subjects: Animals; Aorta - metabolism; Aorta - physiology; Aorta - physiopathology; Arterial hypertension. Arterial hypotension; Biological and medical sciences; Blood and lymphatic vessels; Calcium - pharmacology; Cardiology. Vascular system; Experimental diseases; Hypertension - metabolism; Medical sciences; Membrane Potentials - drug effects; Muscle, Smooth, Vascular - metabolism; Muscle, Smooth, Vascular - physiology; Muscle, Smooth, Vascular - physiopathology; Patch-Clamp Techniques; Peptides - pharmacology; Potassium Channels - biosynthesis; Potassium Channels - drug effects; Potassium Channels - physiology; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Rats, Sprague-Dawley; Reference Values; RNA, Messenger - biosynthesis; Scorpion Venoms - pharmacology; Transcription, Genetic
• ISSN: 0194-911X; 1524-4563
• DOI: 10.1161/01.hyp.30.6.1403

Potassium efflux through Ca -sensitive K channels (KCa channels) is increased in arterial smooth muscle cells from hypertensive rats, but the molecular mechanism is unknown. The goal of this study was to compare the levels of KCa channel current between aortic smooth muscle cells from adult Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) and then use Western blot methods and ribonuclease protection assays to examine the expression and mRNA levels for the KCa channel in these same vascular tissues. Whole-cell patch-clamp methods indicated a larger component of KCa channel current, sensitive to block by iberiotoxin (100 nmol/L), in single aortic smooth muscle cells from SHR compared with WKY. Subsequent Western blot analysis using a site-specific antibody (anti-alpha913-926) directed against the S9/S10 linker of the alpha-subunit of the KCa channel revealed a 125-kD immunoreactive band in lanes loaded with either WKY or SHR aortic muscle membranes. The immunoreactive density of this band, which corresponded to the known molecular size of the alpha-subunit, was 2.2-fold greater in lanes loaded with aortic smooth muscle membranes from the hypertensive animals. However, despite this evidence for an increased expression and functional enhancement of KCa channels in aortic smooth muscle membranes of SHR, ribonuclease protection assays with a () P-labeled riboprobe targeted against the S9/S10 linker of the K (Ca) channel alpha-subunit revealed no difference in mRNA levels for the alpha-subunit between WKY and SHR aortic tissue. These findings provide initial evidence that (1) an increased expression of KCa channels may be a mechanism for the enhanced KCa current in aortic smooth muscle membranes of SHR, and (2) the upregulation of KCa channels in arterial muscle membranes during hypertension, which is regarded as a homeostatic mechanism for buffering vascular excitability, may rely on posttranscriptional events. (Hypertension. 1997;30:1403-1409.)