Cerebral artery sarcoplasmic reticulum Ca²⁺ stores and contractility: Changes with development

To test the hypothesis that sarcoplasmic reticulum (SR) Ca²⁺ stores play a key role in norepinephrine (NE)-induced contraction of fetal and adult cerebral arteries and that Ca²⁺ 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 Ca²⁺ concentration ([Ca²⁺](i)) in the absence and presence of different blockers. In adult MCA, after thapsigargin (10^-6 M), the NE-induced responses of tension and [Ca²⁺](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 Ca²⁺, adult MCA increases in tension and [Ca²⁺](i) were 32 ± 5 and 13 ± 3%, respectively, of control. Fetal cerebral arteries, however, showed essentially no response. Ryanodine (RYN, 3 x 10^-6 to 10^-5 M) resulted in increases in tension and [Ca²⁺](i) in both fetal and adult MCA similar to that seen with NE. For both adult and fetal MCA, the increased tension and [Ca²⁺](i) responses to RYN were essentially eliminated in the presence of zero extracellular Ca²⁺. These findings provide evidence that in fetal MCA, in contrast to those in the adult, SR Ca²⁺ stores are of less importance in NE-induced contraction, with such contraction being almost wholly dependent on Ca²⁺ flux via plasma membrane L-type Ca²⁺ channels. In addition, they suggest that in both adult and fetal MCA, the RYN receptor is coupled to the plasma membrane Ca²⁺-activated K⁺ channel and/or L-type Ca²⁺ channel.