Cerebral artery sarcoplasmic reticulum Ca 2+ stores and contractility: changes with development

• Published in: American journal of physiology. Regulatory, integrative and comparative physiology integrative and comparative physiology, 2000-09, Vol.279 (3), p.R860-R873
• Main Authors: Long, Wen, Zhang, Lubo, Longo, Lawrence D.
• Format: Article
• Language: English
• ISSN: 0363-6119; 1522-1490
• DOI: 10.1152/ajpregu.2000.279.3.R860

To test the hypothesis that sarcoplasmic reticulum (SR) Ca 2+ stores play a key role in norepinephrine (NE)-induced contraction of fetal and adult cerebral arteries and that Ca 2+ stores change with development, we performed the following study. In main branch middle cerebral arteries (MCA) from near-term fetal (∼140 days) and nonpregnant adult sheep, we measured NE-induced contraction and intracellular Ca 2+ concentration ([Ca 2+ ] i ) in the absence and presence of different blockers. In adult MCA, after thapsigargin (10 −6 M), the NE-induced responses of tension and [Ca 2+ ] i were 37 ± 5 and 47 ± 7%, respectively, of control values ( P < 0.01 for each). In the fetal artery, in contrast, this treatment resulted in no significant changes from control. When this was repeated in the absence of extracellular Ca 2+ , adult MCA increases in tension and [Ca 2+ ] i were 32 ± 5 and 13 ± 3%, respectively, of control. Fetal cerebral arteries, however, showed essentially no response. Ryanodine (RYN, 3 × 10 −6 to 10 −5 M) resulted in increases in tension and [Ca 2+ ] i in both fetal and adult MCA similar to that seen with NE. For both adult and fetal MCA, the increased tension and [Ca 2+ ] i responses to RYN were essentially eliminated in the presence of zero extracellular Ca 2+ . These findings provide evidence that in fetal MCA, in contrast to those in the adult, SR Ca 2+ stores are of less importance in NE-induced contraction, with such contraction being almost wholly dependent on Ca 2+ flux via plasma membrane L-type Ca 2+ channels. In addition, they suggest that in both adult and fetal MCA, the RYN receptor is coupled to the plasma membrane Ca 2+ -activated K + channel and/or L-type Ca 2+ channel.