Abstract
The possibility that Ca2+-activated Cl− conductances (CaCCs) contribute to oscillations in vascular tone (vasomotion) is tested in isolated mesenteric small arteries from rats where cGMP independent (I Cl(Ca)) and cGMP-dependent (I Cl(Ca,cGMP)) chloride conductances are important. The effect of anion substitution and Cl− channel blockers on noradrenaline (NA)-stimulated tension in isometrically mounted mesenteric arteries and for chloride conductance of smooth muscle cells isolated from these arteries were assessed electrophysiologically. Cl− o replacement with aspartate blocked vasomotion while 36mM SCN− o (substituted for Cl−) was sufficient to inhibit vasomotion. Oscillations in tone, membrane potential, and [Ca2+]i disappeared with 36mM SCN−. DIDS and Zn2+ blocked I Cl(Ca,cGMP) but not I Cl(Ca). Vasomotion was not sensitive to DIDS and Zn2+, and DIDS and Zn2+ induce vasomotion in arteries without endothelium. The vasomotion in the presence of DIDS and Zn2+ was sensitive to 36mM SCN− o. The anion substitution data indicate that Cl− is crucial for the V m and [Ca2+]i oscillations underlying vasomotion. The Cl− channel blocker data are consistent with both CaCCs being important.
Similar content being viewed by others
References
Large WA, Wang Q (1996) Characteristics and physiological role of the Ca2+-activated Cl− conductance in smooth muscle. Am J Physiol 271:C435–C454
Chipperfield AR, Harper AA (2000) Chloride in smooth muscle. Prog Biophys Mol Biol 74:175–221
Kitamura K, Yamazaki J (2001) Chloride channels and their functional roles in smooth muscle tone in the vasculature. Jpn J Pharmacol 85:351–357
Piper AS, Large WA (2004) Single cGMP-activated Ca2+-dependent Cl− channels in rat mesenteric artery smooth muscle cells. J Physiol 555:397–408
Matchkov VV, Aalkjaer C, Nilsson H (2004) A cyclic GMP-dependent calcium-activated chloride current in smooth-muscle cells from rat mesenteric resistance arteries. J Gen Physiol 123:121–134
Aalkjaer C, Nilsson H (2005) Vasomotion: cellular background for the oscillator and for the synchronization of smooth muscle cells. Br J Pharmacol 144:605–616
Haddock RE, Hill CE (2005) Rhythmicity in arterial smooth muscle. J Physiol 566:645–656
Peng H, Matchkov V, Ivarsen A, Aalkjaer C, Nilsson H (2001) Hypothesis for the initiation of vasomotion. Circ Res 88:810–815
Jacobsen JC, Aalkjaer C, Nilsson H, Matchkov V, Freiberg J, Holstein-Rathlou NH (2007) A model of smooth muscle cell synchronization in the arterial wall. Am J Physiol 293:H229–H237
Mulvany MJ, Halpern W (1977) Contractile properties of small arterial resistance vessels in spontaneously hypertensive and normotensive rats. Circ Res 41:19–26
Aalkjaer C, Cragoe EJ (1988) Intracellular pH regulation in resting and contracting segments of rat mesenteric resistance vessels. J Physiol 402:391–410
Mulvany MJ, Nilsson H, Flatman JA (1982) Role of membrane potential in the response of rat small mesenteric arteries to exogenous noradrenaline stimulation. J Physiol 332:363–373
Nilsson H, Videbaek LM, Toma C, Mulvany MJ (1998) Role of intracellular calcium for noradrenaline-induced depolarization in rat mesenteric small arteries. J Vasc Res 35:36–44
Matchkov VV, Aalkjaer C, Nilsson H (2005) Distribution of cGMP-dependent and cGMP-independent Ca2+-activated Cl− conductances in smooth muscle cells from different vascular beds and colon. Pflugers Arch 451:371–379
Matchkov VV, Rahman A, Bakker LM, Griffith TM, Nilsson H, Aalkjaer C (2006) Analysis of effects of connexin-mimetic peptides in rat mesenteric small arteries. Am J Physiol Heart Circ Physiol 291:H357–H367
Chaytor AT, Evans WH, Griffith TM (1997) Peptides homologous to extracellular loop motifs of connexin 43 reversibly abolish rhythmic contractile activity in rabbit arteries. J Physiol 503:99–110
Matchkov VV, Rahman A, Peng H, Nilsson H, Aalkjaer C (2004) Junctional and nonjunctional effects of heptanol and glycyrrhetinic acid derivates in rat mesenteric small arteries. Br J Pharmacol 142:961–972
Gustafsson H, Nilsson H (1993) Rhythmic contractions of isolated small arteries from rat: role of calcium. Acta Physiol Scand 149:283–291
Aalkjaer C, Hughes A (1991) Chloride and bicarbonate transport in rat resistance arteries. J Physiol 436:57–73
Qu Z, Hartzell HC (2001) Functional geometry of the permeation pathway of Ca2+-activated Cl− channels inferred from analysis of voltage-dependent block. J Biol Chem 276:18423–18429
Piper AS, Greenwood IA, Large WA (2002) Dual effect of blocking agents on Ca2+-activated Cl− currents in rabbit pulmonary artery smooth muscle cells. J Physiol 539:119–131
Jacobsen JC, Aalkjaer C, Nilsson H, Matchkov V, Freiberg J, Holstein-Rathlou NH (2007) Activation of a cGMP-sensitive calcium-dependent chloride channel may cause transition from calcium waves to whole-cell oscillations in smooth muscle cells. Am J Physiol 293:H215–H228
Dawson DC, Smith SS, Mansoura MK (1999) CFTR: mechanism of anion conduction. Physiol Rev 79:S47–S75
Greenwood IA, Ledoux J, Leblanc N (2001) Differential regulation of Ca2+-activated Cl- currents in rabbit arterial and portal vein smooth muscle cells by Ca2+-calmodulin-dependent kinase. J Physiol 534:395–408
Saleh SN, Greenwood IA (2005) Activation of chloride currents in murine portal vein smooth muscle cells by membrane depolarization involves intracellular calcium release. Am J Physiol Cell Physiol 288:C122–C131
Amedee T, Large WA, Wang Q (1990) Characteristics of chloride currents activated by noradrenaline in rabbit ear artery cells. J Physiol 428:501–516
Greenwood IA, Leblanc N (2007) Overlapping pharmacology of Ca2+-activated Cl- and K+ channels. Trends Pharmacol Sci 28:1–5
Acknowledgements
The current work was supported by grants from Lundbeck and the Karen Elise Jensen fund. Donna Briggs Boedtkjer was supported by a Ph.D. stipend from the Danish Cardiovascular Research Academy. The authors wish to acknowledge the technical assistance provided by Kirsten Skaarup, Jørgen Andresen, and Trine Rohde.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Boedtkjer, D.M.B., Matchkov, V.V., Boedtkjer, E. et al. Vasomotion has chloride-dependency in rat mesenteric small arteries. Pflugers Arch - Eur J Physiol 457, 389–404 (2008). https://doi.org/10.1007/s00424-008-0532-3
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00424-008-0532-3