Distinct Pathways of Ca2+Sensitization in Porcine Coronary ArteryEffects of Rho-Related Kinase and Protein Kinase C Inhibition on Force and Intracellular Ca2+
作者:
Koji,
Nobe Richard,
期刊:
Circulation Research: Journal of the American Heart Association
(OVID Available online 2001)
卷期:
Volume 88,
issue 12
页码: 1283-1290
ISSN:0009-7330
年代: 2001
出版商: OVID
关键词: coronaryarteries;Ca2+sensitization;protein kinaseC;Rho-kinase;U46619
数据来源: OVID
摘要:
Alterationsof the Ca2+sensitivity of contraction havebeen reported for porcine coronary artery, but the mechanisms are not clearlyunderstood. We investigated the mechanism(s) ofCa2+sensitization in response to thethromboxane A2analogue (U46619). Our hypothesis isthat different mechanisms of Ca2+sensitization could be distinguished by their distinct time courses.Therefore, we measured the time course of[Ca2+]iandisometric force simultaneously in an intact artery after a single addition ofU46619. The initial transient phase was associated withCa2+release from the sarcoplasmic reticulum,whereas the maintained phase was associated withCa2+influx. Two distinct types ofCa2+sensitization characterized these phaseswith either protein kinase C (PKC)-mediated or Rho-kinase-mediated mechanisms.Their effects were quite distinct on the basis of the time courses over whichthe sensitization was effective. PKC inhibition (1 &mgr;mol/L calphostin C)had a much greater effect in the initial phase, diminishing the size of thetransient and prolonging the rise in force and the decline in[Ca2+]i.There were limited effects on the sustained force. Rho-kinase inhibition (10&mgr;mol/L Y27632), in contrast, nearly abolished the sustained force but hada lesser effect on the transient phase. Neither inhibitor had any effect onthe force versus[Ca2+]irelations for KCl contractures. Our evidence suggests that both PKC-mediatedand Rho-kinase-mediated Ca2+sensitizationsare present in coronary arteries, but the latter is dominant in thromboxaneA2receptor-mediatedcontraction.
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