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• W2173955148 endingPage "R2014" @default.
• W2173955148 startingPage "R2004" @default.
• W2173955148 abstract "The present study was designed to test the hypothesis that in cerebral arteries of the fetus, ATP-sensitive (K ATP ) and Ca 2+ -activated K + channels (K Ca ) play an important role in the regulation of intracellular Ca 2+ concentration ([Ca 2+ ] i ) and that this differs significantly from that of the adult. In main branch middle cerebral arteries (MCA) from near-term fetal (∼140 days) and nonpregnant adult sheep, simultaneously we measured norepinephrine (NE)-induced responses of vascular tension and [Ca 2+ ] i in the absence and presence of selective K + -channel openers/blockers. In fetal MCA, in a dose-dependent manner, both the K ATP -channel opener pinacidil and the K Ca -channel opener NS 1619 significantly inhibited NE-induced tension [negative logarithm of the half-maximal inhibitory concentration (pIC 50 ) = 5.0 ± 0.1 and 8.2 ± 0.1, respectively], with a modest decrease of [Ca 2+ ] i . In the adult MCA, in contrast, both pinacidil and NS 1619 produced a significant tension decrease (pIC 50 = 5.1 ± 0.1 and 7.6 ± 0.1, respectively) with no change in [Ca 2+ ] i . In addition, the K Ca -channel blocker iberiotoxin (10 −7 to 10 −6 M) resulted in increased tension and [Ca 2+ ] i in both adult and fetal MCA, although the K ATP -channel blocker glibenclamide (10 −7 to 3 × 10 −5 M) failed to do so. Of interest, administration of 10 −7 M iberiotoxin totally eliminated vascular contraction and increase in [Ca 2+ ] i seen in response to 10 −5 M ryanodine. In precontracted fetal cerebral arteries, activation of the K ATP and K Ca channels significantly decreased both tension and [Ca 2+ ] i , suggesting that both K + channels play an important role in regulating L-type channel Ca 2+ flux and therefore vascular tone in these vessels. In the adult, K ATP and the K Ca channels also appear to play an important role in this regard; however, in the adult vessel, activation of these channels with resultant vasorelaxation can occur with no significant change in [Ca 2+ ] i . These channels show differing responses to inhibition, e.g., K Ca -channel inhibition, resulting in increased tension and [Ca 2+ ] i , whereas K ATP -channel inhibition showed no such effect. In addition, the K Ca channel appears to be coupled to the sarcoplasmic reticulum ryanodine receptor. Thus differences in plasma membrane K + -channel activity may account, in part, for the differences in the regulation of contractility of fetal and adult cerebral arteries." @default.
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• W2173955148 date "2000-12-01" @default.
• W2173955148 modified "2023-10-18" @default.
• W2173955148 title "Cerebral artery K_ATP- and K_Ca-channel activity and contractility: changes with development" @default.
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• W2173955148 doi "https://doi.org/10.1152/ajpregu.2000.279.6.r2004" @default.
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