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This Article Full Text Full Text (PDF) All Versions of this Article: 286/6/H2287    most recent 00739.2003v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (4) Citing Articles via Google Scholar Google Scholar Articles by Ferrusi, I. Articles by von der Weid, P.-Y. Search for Related Content PubMed PubMed Citation Articles by Ferrusi, I. Articles by von der Weid, P.-Y.

Cyclopiazonic acid decreases spontaneous transient depolarizations in guinea pig mesenteric lymphatic vessels in endothelium-dependent and -independent manners

¹Mucosal Inflammation and Smooth Muscle Research Groups, Department of Physiology and Biophysics, Faculty of Medicine, University of Calgary, Alberta, Canada T2N 4N1; and ²Neuroscience Group, School of Biomedical Sciences, Faculty of Health, University of Newcastle, Callaghan, New South Wales, Australia 2308

Submitted 4 August 2003 ; accepted in final form 26 January 2004

Guinea pig mesenteric lymphatic vessels exhibit vasomotion through a pacemaker mechanism that involves intracellular Ca²⁺ release and resultant spontaneous transient depolarizations (STDs) of the smooth muscle membrane potential. This study presents a detailed characterization of the effects of cyclopiazonic acid (CPA) on this pacemaker activity. Microelectrode recordings from smooth muscle in vessel segments revealed that application of CPA (1–10 µM) caused a hyperpolarization accompanied by a decrease in the frequency and amplitude of STDs. The CPA-induced hyperpolarization was abolished after destruction of the endothelium and in the presence of N^G-nitro-L-arginine (100 µM) or 1H-[1,2,4]oxadiazolol-[4,3-a]quinoxaline-1-one (10 µM), which suggests a contribution of endothelium-derived nitric oxide (EDNO) in this response. In the absence of EDNO-induced effects, CPA decreased the frequency and amplitude of STDs recorded before and in the presence of the thromboxane A₂ mimetic U-46619, norepinephrine, or thimerosal. CPA abolished U-46619-induced vasomotion as determined by measurement of constriction-associated intracellular Ca²⁺ concentration using the ratiometric Ca²⁺ indicator fura-2. The endothelial actions of CPA were compared with those of ACh, which is known to cause EDNO release in this preparation. Although CPA and ACh both increased endothelial intracellular Ca²⁺ concentration and depolarized the membrane potential, the kinetics of action for both parameters were markedly slower for CPA than ACh. These results suggest that CPA first hyperpolarizes the lymphatic smooth muscle and decreases STD frequency and amplitude through endothelial release of EDNO, and second, consistent with the action of CPA to inhibit sarcoplasmic reticulum Ca²⁺-ATPase and deplete Ca²⁺ stores, it further reduces STD activity. Inhibition of the lymphatic smooth muscle pacemaker mechanism is thought to abolish agonist-induced vasomotion.

pumping; nitric oxide; smooth muscle; lymphatic vasomotion

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				M. S. Imtiaz, J. Zhao, K. Hosaka, P.-Y. von der Weid, M. Crowe, and D. F. van Helden Pacemaking through Ca2+ Stores Interacting as Coupled Oscillators via Membrane Depolarization Biophys. J., June 1, 2007; 92(11): 3843 - 3861. [Abstract] [Full Text] [PDF]