Abstract
Ablation of the premigratory cardiac neural crest (CNC) from the chick embryo results in a malformed outflow tract vasculature termed persistent truncus arteriosus (PTA). In addition, loss of the CNC disrupts myocardial excitation–contraction (EC) coupling, decreases intracellular Ca2+ transients, and depresses force generation. We examined if similar defects occurred in the neural crest-derived smooth muscle of the aortic arch in a test of the hypothesis that loss of elements from the CNC disrupts EC coupling and force production in the smooth muscle of the tunica media of the aortic arch. Aortic arch segments from chicks (embryonic day 15) displaying PTA generated ~43% of stress generated by the aortic arch from sham-operated control embryos during potassium depolarization. The depressed force response was associated with a twofold lower Fura-2 transient. In contrast, force and steady-state Fura-2 signals during endothelin-1 stimulation were unchanged. The differences seen in stress generation with potassium depolarization between sham and PTA displaying embryos were not seen in the descending aorta, a tissue not derived from the neural crest. Protein content and immunostaining revealed no differences in the content of actin, myosin, or dihydropyridine receptor from sham or PTA aortic arch. Our results suggest that the CNC is required for normal aortic arch smooth muscle function and support the hypothesis that the loss of CNC impacts the force generating ability, in part by disruption of the EC-coupling processes and altering Ca2+-handling.
Similar content being viewed by others
References
Aiba S and Creazzo TL (1992) Calcium currents in hearts with persistent truncus arteriosus. Am J Physiol 262: H1182-H1190.
Bergwer. M, Verberne ME, DeRuiter MC, Poelmann RE, and Gittenberger-de Groot AC (1998) Neural crest cell contribution to the developing circulatory system: implications for vascular morphology? Circ Res 82: 221-231.
Berk BC, Canessa M, Vallega G and Alexander RW (1988) Agonist-mediated changes in intracellular pH: role in vascular smooth muscle cell function. J Cardiovasc Pharmacol 12(Suppl 5): S104-S114.
Boyarsky G, Hanssen C and Clyne LA (1996a) Inadequacy of high K+/nigericin for calibrating BCECF. I. Estimating steady-state intracellular pH. Am J Physiol 271: C1131-C1145.
Boyarsky G, Hanssen C and Clyne LA (1996b) Inadequacy of high K+/nigericin for calibrating BCECF. II. Intracellular pH dependence of the correction. Am J Physiol 271: C1146-C1156.
Boyarsky G, Hanssen C and Clyne LA (1996c) Superiority of in vitro over in vivo calibrations of BCECF in vascular smooth muscle cells. FASEB J 10: 1205-1212.
Brotto MA and Creazzo TL (1996) Ca2+ transients in embryonic chick heart: contributions from Ca2+ channels and the sarcoplasmic reticulum. Am J Physiol 270: H518-H525.
Couly G, Grapin-Botton A, Coltey P and Le Douarin NM (1996) The regeneration of the cephalic neural crest, a problem revisited: the regenerating cells originate from the contralateral or from the anterior and posterior neural fold. Development 122: 3393-3407.
Creazzo TL (1990) Reduced L-type calcium current in the embryonic chick heart with persistent truncus arteriosus. Circ Res 66: 1491-1498.
Creazzo TL, Brotto MA and Burch J (1997) Excitation-contraction coupling in the day 15 embryonic chick heart with persistent truncus arteriosus. Pediatr Res 42: 731-737.
Creazzo TL, Godt RE, Leatherbury L, Conway SJ and Kirby ML (1998) Role of cardiac neural crest cells in cardiovascular development. Ann Rev Physiol 60: 267-286.
Daugirdas JT, Arrieta J, Ye M, Flores G and Battle DC (1995) Intracellular acidi.cation associated with changes in free cytosolic calcium. Evidence for Ca2+/H+ exchange via a plasma membrane Ca(2+)-ATPase in vascular smooth muscle cells. J Clin Invest 95: 1480-1489.
Decker ER and Brock TA (1998) Endothelin and Calcium Signaling, In: Pollock DM and Highsmith RF (eds) Endothelin Receptors and Signaling Mechanisms. (pp. 131-146) Springer-Verlag, Berlin.
Edmonds LD and James LM (1993) Temporal trends in the birth prevalence of selected congenital malformations in the Birth Defects Monitoring Program/Commission on Professional and Hospital Activities, 1979-1989. Teratology 48: 647-649.
Fukiishi Y and Morriss K (1992) Migration of cranial neural crest cells to the pharyngeal arches and heart in rat embryos. Cell Tissue Res 268: 1-8.
Gadson PF, Rossignol C, McCoy J and Rosenquist TH (1993) Expression of elastin, smooth muscle alpha-actin, and c-jun as a function of the embryonic lineage of vascular smooth muscle cells. In Vitro Cell Dev Biol Anim 29A: 773-781.
Hofmann F and Klugbauer N (1996) Molecular Biology and Expression of Smooth Muscle L-type calcium Channels, In: Bárány M (ed.) Biochemistry of Smooth Muscle Contraction. (pp. 221-226) Academic Press, Inc., San Diego.
Hungerford JE and Little CD (1999) Developmental biology of the vascular smooth muscle cell: building a multilayered vessel wall. J Vasc Res 36: 2-27.
Keith TL and Highsmith RF (1998) Endothelin and Ion Channels, In: Pollock DM and Highsmith RF (eds) Endothelin Receptors and Signaling Mechanisms. (pp. 115-129) Springer-Verlag, Berlin.
Kirby ML, Gale TF and Stewart DE (1983) Neural crest cells contribute to normal aorticopulmonary septation. Science 220: 1059-1061.
Kirby ML, Kumiski DH, Myers T, Cerjan C and Mishima N (1993) Backtransplantation of chick cardiac neural crest cells cultured in LIF rescues heart development. Dev Dyn 198: 296-311.
Kirby ML, Turnage KL and Hays BM (1985) Characterization of conotruncal malformations following ablation of 'cardiac' neural crest. Anat Rec 213: 87-93.
Kirby ML and Waldo KL (1995) Neural crest and cardiovascular patterning. Circ Res 77: 211-215.
Koh E, Morimoto S, Kim S, Nabata T, Miyashita Y and Ogihara T (1990) Endothelin stimulates Na+/H+ exchange in vascular smooth muscle cells. Biochem Int 20: 375-380.
le Noble FA, Ruijtenbeek K, Gommers S, De Mey JG and Blanco CE (2000) Contractile and relaxing reactivity in carotid and femoral arteries of chicken embryos. Am J Physiol Heart Circ Physiol 278: H1261-H1268.
Leatherbury L, Connuck DM, Gauldin HE and Kirby ML (1991) Hemodynamic changes and compensatory mechanisms during early cardiogenesis after neural crest ablation in chick embryos. Pediatr Res 30: 509-512.
Majesky MW, Benditt EP and Schwartz SM (1988) Expression and developmental control of platelet-derived growth factor A-chain and B-chain/Sis genes in rat aortic smooth muscle cells. Proc Natl Acad Sci USA 85: 1524-1528.
Majesky MW, Giachelli CM, Reidy MA and Schwartz SM (1992) Rat carotid neointimal smooth muscle cells reexpress a developmentally regulated mRNA phenotype during repair of arterial injury. Circ Res 71: 759-768.
Nagesetty R and Paul RJ (1994) Effects of pH on isometric force and [Ca2+]i in porcine coronary artery smooth muscle. Circ Res 75: 990-998.
Nosek TM, Fogaca RT, Hatcher CJ, Brotto MA and Godt RE (1997) Effect of cardiac neural crest ablation on contractile force and calcium uptake and release in chick heart. Am J Physiol 273: H1464-H1471.
Owens GK (1995) Regulation of differentiation of vascular smooth muscle cells. Physiol Rev 75: 487-517.
Rosenquist TH and Beall AC (1990) Elastogenic cells in the developing cardiovascular system. Smooth muscle, nonmuscle, and cardiac neural crest. Ann N Y Acad Sci 588: 106-119.
Rosenquist TH, Beall AC, Modis L and Fishman R (1990) Impaired elastic matrix development in the great arteries after ablation of the cardiac neural crest. Anat Rec 226: 347-359.
Rosenquist TH, Kirby ML and van Mierop LH (1989) Solitary aortic arch artery. A result of surgical ablation of cardiac neural crest and nodose placode in the avian embryo. Circulation 80: 1469-1475.
Siczkowski M, Quinn PA and Ng LL (1997) Calcium-induced activation of the rat vascular myocyte Na+/H+ exchanger isoform-1. Metabolism 46: 250-256.
Stewart DE, Kirby ML and Sulik KK (1986) Hemodynamic changes in chick embryos precede heart defects after cardiac neural crest ablation. Circ Res 59: 545-550.
Topouzis S and Majesky MW (1996) Smooth muscle lineage diversity in the chick embryo. Two types of aortic smooth muscle cell differ in growth and receptor-mediated transcriptional responses to transforming growth factor-beta. Dev Biol 178: 430-445.
Waldo K, Zdanowicz M, Burch J, Kumiski DH, Stadt HA, Godt RE, Creazzo TL and Kirby ML (1999) A novel role for cardiac neural crest in heart development. J Clin Invest 103: 1499-1507.
Wray S (1988) Smooth muscle intracellular pH: measurement, regulation, and function. Am J Physiol 254: C213-C225.
Wrenn RW, Raeuber CL, Herman LE, Walton WJ and Rosenquist TH (1993) Transforming growth factor-beta: signal transduction via protein kinase C in cultured embryonic vascular smooth muscle cells. In Vitro Cell Dev Biol 29A: 73-78.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Wingard, C.J., Godt, R.E. Cardiac neural crest ablation alters aortic smooth muscle force and voltage-sensitive Ca2+ responses. J Muscle Res Cell Motil 23, 293–303 (2002). https://doi.org/10.1023/A:1022081123578
Issue Date:
DOI: https://doi.org/10.1023/A:1022081123578