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Biochem Biophys Res Commun. 2014 Feb 28;445(1):84-8. doi: 10.1016/j.bbrc.2014.01.150. Epub 2014 Feb 4.

Calcium oscillations in human mesenteric vascular smooth muscle.

Author information

1
Departamento de Farmacología, Universidad Complutense, av. Séneca 2, 28040 Madrid, Spain.
2
Department of Anesthesiology, Pharmacology, and Therapeutics, The University of British Columbia, 2176 Health Sciences Mall, Medical Block C, Vancouver, BC V6T 1Z3, Canada.
3
Department of Anesthesiology, Pharmacology, and Therapeutics, The University of British Columbia, 2176 Health Sciences Mall, Medical Block C, Vancouver, BC V6T 1Z3, Canada. Electronic address: nicola.fameli@ubc.ca.

Abstract

Phenylephrine (PE)-induced oscillatory fluctuations in intracellular Ca(2+) concentration ([Ca(2+)]i) of vascular smooth muscle have been observed in many blood vessels isolated from a wide variety of mammals. Paradoxically, until recently similar observations in humans have proven elusive. In this study, we report for the first time observations of adrenergically-stimulated [Ca(2+)]i oscillations in human mesenteric artery smooth muscle. In arterial segments preloaded with Fluo-4 AM and mounted on a myograph on the stage of a confocal microscope, we observed PE-induced oscillations in [Ca(2+)]i, which initiated and maintained vasoconstriction. These oscillations present some variability, possibly due to compromised health of the tissue. This view is corroborated by our ultrastructural analysis of the cells, in which we found only (5 ± 2)% plasma membrane-sarcoplasmic reticulum apposition, markedly less than measured in healthy tissue from laboratory animals. We also partially characterized the oscillations by using the inhibitory drugs 2-aminoethoxydiphenyl borate (2-APB), cyclopiazonic acid (CPA) and nifedipine. After PE contraction, all drugs provoked relaxation of the vessel segments, sometimes only partial, and reduced or inhibited oscillations, except CPA, which rarely caused relaxation. These preliminary results point to a potential involvement of the sarcoplasmic reticulum Ca(2+) and inositol 1,4,5-trisphosphate receptor (IP3R) in the maintenance of the Ca(2+) oscillations observed in human blood vessels.

KEYWORDS:

2-APB; CPA; Calcium oscillations; ER junctions; Human smooth muscle; IP(3) receptors; Mesenteric artery; Nifedipine; Sarcoplasmic reticulum

PMID:
24508261
DOI:
10.1016/j.bbrc.2014.01.150
[Indexed for MEDLINE]
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