© 2000 by European Society of Cardiology
Copyright © 2000, European Society of Cardiology
Role of Ca2+- and swelling-activated Cl– channels in 
1-adrenoceptor-mediated tone in pressurized rabbit mesenteric arterioles
Department of Physiology, University of Montréal and Montréal Heart Institute Research Centre, 5000 East Bélanger St., Montreal, Quebec, Canada H1T 1C8
* Corresponding author. Tel.: +1-514-376-3330; fax: +1-514-376-1355 leblancn{at}alize.ere.umontreal.ca
Background: Ca2+-activated (ICl(Ca)) and swelling-induced (ICl(swell)) Cl– channels have, respectively, been postulated to participate in the membrane depolarization and contraction mediated by activation of 
1-adrenoceptors and vascular wall distension during pressurization. Their respective function in generating active force in pressurized arterioles during 1-adrenoceptor stimulation remains unsettled. Objectives: Experimental protocols were designed to: (1) assess the relative contribution of ICl(Ca) to the pressure-dependence of lumen diameter of mesenteric arterioles at different states of activation of the 1-adrenoceptor, and (2) investigate the potential role of ICl(swell) in spontaneous and agonist-mediated myogenic reactivity. Methods: Segments of endothelium-denuded rabbit mesenteric arterioles with a lumen diameter of 
70 µm were cannulated at both ends and studied under isobaric conditions at 36°C. Steady-state lumen diameter at each pressure step investigated (0–100 mmHg, in 20-mmHg increments) was measured by a video-microscopy edge-detection technique. Results: Under control conditions, 23% of the arterioles developed nifedipine-sensitive spontaneous myogenic tone. In the presence of 1 mM tetraethylammonium chloride (TEA) to inhibit Ca2+-dependent K+ channels, the 1-agonist phenylephrine (PE) contracted the vessels in a concentration-dependent manner (0.1–10 µM) and potentiated myogenic reactivity. The contraction mediated by 1 µM PE/TEA was abolished by 1 µM nifedipine, indicating that Ca2+ entry through voltage-gated Ca2+ channels was a necessary step in the cascade leading to contraction. Niflumic acid (NfA, 100 µM), a relatively selective inhibitor of ICl(Ca), had no effect on myogenic tone but reversed the PE-induced contraction, varying with the concentration of PE and transmural pressure. For PE concentrations between 0.1 and 1 µM, but not for 10 µM PE, the relaxing efficacy of NfA decreased as applied pressure was raised from 0 to 100 mmHg. At all pressure steps, the NfA-induced relaxation was inversely related to the concentration of PE. DIDS (200 µM), another Cl– channel blocker, inhibited spontaneous myogenic tone, and partially suppressed a component of contraction at elevated transmural pressures in arterioles incubated in 1 µM PE/1 mM TEA/100 µM NfA. Conclusions: Our data indicate that under low to moderate stimulation of the 1-adrenoceptor signaling pathway, ICl(Ca) channels play an important role in the sustained contraction produced. Their declining contribution to contraction with increasing transmural pressure may be explained, at least in part, by a progressive enhancement of stretch-induced ionic conductances, possibly volume-sensitive Cl– channels.
KEYWORDS Adrenergic (ant)agonists, Cl-channel, Smooth muscle; Stretch/m-e coupling; Vasoconstriction/dilation
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  J. Ledoux, I. Greenwood, L. R Villeneuve, and N. Leblanc Modulation of Ca2+-dependent Cl- channels by calcineurin in rabbit coronary arterial myocytes J. Physiol., November 1, 2003; 552(3): 701 - 714. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. A Greenwood, J. Ledoux, and N. Leblanc Differential regulation of Ca2+-activated Cl- currents in rabbit arterial and portal vein smooth muscle cells by Ca2+-calmodulin-dependent kinase J. Physiol., July 15, 2001; 534(2): 395 - 408. [Abstract] [Full Text] [PDF]
|
|