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Differential effects of hypoxia on the intracellular Ca2+ concentration of myocytes isolated from different regions of the rat pulmonary arterial tree.

Abstract
Hypoxic pulmonary vasoconstriction (HPV) may be mediated, in part, by an oxygen-sensing mechanism intrinsic to pulmonary arterial smooth muscle. It has been proposed that hypoxia inhibits a K+ conductance, which promotes membrane depolarization, subsequent activation of L-type Ca2+ channels and ultimately constriction. We have monitored hypoxia-induced changes in the intracellular Ca2+ concentration ([Ca2+]i) of single myocytes isolated from the rat pulmonary arterial tree using microspectrofluorimetry and ratiometric measurement of indo-1 fluorescence. The basal level of [Ca2+]i was in the range 35-80 nM and cells were quiescent at rest exhibiting no spontaneous oscillations in [Ca2+]i. When the extracellular K+ concentration ([K+]o) was raised to 20 mM, the [Ca2+]i increased from approximately 60 to approximately 100 nM. This increase was abolished by nifedipine, demonstrating the presence, and need for activation, of functional voltage-gated L-type Ca2+ channels. Hypoxia (PO2 < or = 30 mmHg; throughout) had little effect on the resting [Ca2+]i in myocytes isolated from either the main intrapulmonary artery, or its primary, secondary or tertiary branches. However, upon raising the [Ca2+]i by increasing [K+]o to 20 mM, hypoxia was found to lower [Ca2+]i from approximately 110 to approximately 70 nM, in cells isolated from the main conduit and primary branches of the intrapulmonary artery. In marked contrast, when [Ca2+]i was raised, by increasing [K+]o to 20 mM, in myocytes isolated from secondary and tertiary branches of the intrapulmonary artery, hypoxia induced a further reversible increase in the [Ca2+]i from approximately 160 to approximately 240 nM. Neither hypoxia alone nor in combination with 20 mM K(+)o induced any increase in the [Ca2+]i in the presence of nifedipine. We conclude that hypoxia may modulate [Ca2+]i in rat pulmonary artery myocytes only following its elevation by a depolarizing stimulus.
AuthorsA Bakhramov, A M Evans, R Z Kozlowski
JournalExperimental physiology (Exp Physiol) Vol. 83 Issue 3 Pg. 337-47 (May 1998) ISSN: 0958-0670 [Print] England
PMID9639343 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Calcium
Topics
  • Animals
  • Calcium (metabolism)
  • Cell Separation
  • Homeostasis (physiology)
  • Hypoxia (metabolism)
  • Intracellular Membranes (metabolism)
  • Male
  • Muscle, Smooth, Vascular (cytology, metabolism)
  • Osmolar Concentration
  • Pulmonary Artery (cytology, metabolism)
  • Rats
  • Rats, Wistar

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