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The effects of the KCNQ potassium channel blocker XE991 on mouse aorta excitabilty KCNQ channels form part of the cardiac action potential and have been implicated in a number of hereditary arrhythmias. Recent studies have identified that KCNQ are expressed in murine portal vein smooth muscle cells (Ohya et al., 2003) and contribute to the resting membrane potential (Yeung & Greenwood, 2005). The aim of the present study was to determine if KCNQ channels influenced vascular tone in murine aorta. Segments of thoracic and abdominal aortae were dissected from female BALB-c mice (6-8 weeks) sacrificed by cervical dislocation and suspended for isometric tension recording in a wire myograph. All tissues were bathed in conventional Krebs solution at 37 ° C and aerated by 95%O2 / 5%CO2. All data are the mean of n segments from N animals ± s.e.m. After an initial equilibration period, 60 mM KCl was applied to tissues to assess tissue viability. The responses to KCl ranged in amplitude from 1-8mN but were greater in the segments closest to the aortic arch relative to segments nearer to the diaphragm. The segments nearest the heart also had a tendency to spontaneously contract. Application of XE991 (0.1-10 μM) to segments of thoracic aortae produced a contractile response in 42 out of 73 segments (N=31) and the degree of contraction was proportional to the contraction produced by KCl. The mean evoked contraction was not significantly different for the concentrations studied 0.54 ± 0.17mN, 0.85 ± 0.25mN, and 0.39 ± 0.05mN for 0.1, 1 and 10 μM, respectively. In 30/42 tissues the response to XE991 was sustained and was rapidly abolished by application of 1 µM nicardipine (n=4) or 1 mM CdCl2 (n=2). In 12/42 tissues the responses to XE991 waned after the initial peak either completely (n=6) or to a sustained level approximately 48% of the peak (n=6). XE991 also provoked contractions in some but not all segments of abdominal aortae with a mean contraction of 1.612 ± 0.97mN produced by 1μM XE991 (n= 4 from 7). The effects of XE991 on the thoracic and abdominal aorta were also tested in the presence and absence of angiotensin-II (ATII). The abdominal aorta segments were more sensitive to ATII than thoracic segments (mean contraction produced by 10 nM ATII was 1.627 ± 0.62mN and 0.20 ± 0.11mN, respectively, n=3-5). In all aortic segments there was an inverse relationship between the amplitude of the ATII evoked response and the subsequent XE991 response. These data provide the first evidence that KCNQ channels may contribute to controlling membrane excitability in aortic vessels from different anatomical locations.
Ohya et al., (2003). Circ Res. 92, 1016-1023. |
