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 cere bral arteries and that Ca2+ stores change with development, we performed th e following study. In main branch middle cerebral arteries (MCA) from near- term fetal (similar to 140 days) and nonpregnant adult sheep, we measured N E-induced contraction and intracellular Ca2+ concentration ([Ca2+](i)) in t he absence and presence of different blockers. In adult MCA, after thapsiga rgin (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). I n the fetal artery, in contrast, this treatment resulted in no significant changes from control. When this was repeated in the absence of extracellula r Ca2+, adult MCA increases in tension and [Ca2+](i) were 32 +/- 5 and 13 /- 3%, respectively, of control. Fetal cerebral arteries, however, showed e ssentially 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 z ero 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 dependen t 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 th e plasma membrane Ca2+-activated K+ channel and/or L-type Ca2+ channel.