Maturation alters the contribution of potassium channels to resting and 5HT-induced tone in small cerebral arteries of the sheep.
To address the hypothesis that maturation alters the contribution of K-channels to resting and agonist-induced tone in small cerebral arteries, second branch middle cerebral arteries (approximately 200 microm) were taken from term fetal (139-141 days gestation) and adult sheep, denuded of endothelium, and mounted in myographs. After determination of length-tension relations, the arteries were stretched to 55, 100, and 145% of optimum length. At each level of stretch, contractile responses to 5 mM 4-aminopyridine (4-AP, voltage-sensitive K-channel blocker), 100 nM iberiotoxin (calcium-sensitive K-channel blocker), 10 microM glibenclamide (ATP-sensitive K-channel blocker), or 10 microM Ba(2+) (inward rectifier K-channel blocker) were recorded. In separate experiments, concentration--response relations were determined for 5-HT in the presence and absence of each of the four K-channel blockers at the same concentrations. Both 4-AP and iberiotoxin produced stretch-dependent contractions of greater magnitude in adult (37% for 4-AP and 43% for iberiotoxin at 100% optimum) than in fetal (5% for 4-AP and 7% for iberiotoxin at 100% optimum) arteries. 4-AP also enhanced the pD(2) for 5-HT in adult (from 7.15 to 7.49), but not in fetal, arteries. Conversely, glibenclamide attenuated the pD(2) for 5-HT in fetal (from 7.02 to 6.71), but not in adult, arteries. Iberiotoxin enhanced the pD(2) for 5-HT in both fetal (from 7.05 to 7.51) and adult (from 7.15 to 7.75) arteries. In addition, iberiotoxin enhanced maximum responses to 5-HT (from 59 to 82%) in adult but not fetal arteries. Finally, 4-AP enhanced the maximum responses to 5-HT in both fetal (from 67 to 85%) and adult (from 59 to 79%) arteries. These results indicate that maturation modulates the contribution of K(V), K(Ca), and K(ATP), but not K(IR) channels to basal and/or 5HT-induced cerebrovascular tone, and demonstrate that K(V) and K(Ca) channels are coupled to stretch-sensitive receptors, and that K(V) and K(Ca) limit contractile responses to 5-HT. To the extent that changes in pD(2) values reflect changes in agonist--ligand interactions, the data also suggest that K(V), K(Ca), and K(ATP) channels may possibly influence ligand--receptor binding for 5-HT.
Teng
Guo Qi
GQ
Center for Perinatal Biology, Department of Physiology, Loma Linda University School of Medicine, Loma Linda, CA 92350, USA.
Nauli
Surya M
SM
Brayden
Joseph E
JE
Pearce
William J
WJ
D000375:Aging / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000098:blood supply / Q000254:growth & development* / Q000378:metabolism; D002536:Cerebral Arteries / Q000187:drug effects / Q000254:growth & development* / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005333:Fetus; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009129:Muscle Tonus / Q000187:drug effects / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000254:growth & development* / Q000378:metabolism; D011188:Potassium / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D011247:Pregnancy; D012701:Serotonin / Q000378:metabolism* / Q000494:pharmacology; D012756:Sheep; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology
D026902:Potassium Channel Blockers; D015221:Potassium Channels; D012701:Serotonin; D011188:Potassium