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Articles in PresS, published online ahead of print August 9, 2002
Am J Physiol Lung Cell Mol Physiol, 10.1152/ajplung.00104.2002
Submitted on April 17, 2002
Accepted on July 13, 2002
1 Staff Anesthesiologist, Justus-Liebig-University, Giessen, Germany
2 Research Associate, VA Medical Center, Minneapolis, USA
3 Scientist, VA Medical Center, Minneapolis, USA
4 Chief of Cardiology, VA Medical Center, Minneapolis, USA
* To whom correspondence should be addressed. E-mail: weirx002{at}tc.umn.edu.
Many studies indicate that hypoxic inhibition of some potassium channels in the membrane of the pulmonary arterial smooth muscle cells (PASMCs) plays a part in initiating hypoxic pulmonary vasoconstriction. The sensitivity of the potassium current (Ik), resting membrane potential (Em) and intracellular [Ca2+] ([Ca2+]i) of PASMCs to different levels of hypoxia in these cells has not been fully explored. Reducing pO2 levels gradually inhibited steady-state Ik of rat resistance PASMCs and depolarized the cell membrane. The block of Ik by hypoxia was voltage-dependent, in that low oxygen tensions (3% and 0% O2) inhibited Ik more at 0mV and -20 mV, than at 50 mV. As expected, the hypoxia-sensitive Ik was also 4-aminopyridinepyridine-sensitive. Fura-2 loaded PASMCs showed a graded increase in [Ca2+]i as pO2 levels declined. This increase was markedly reduced by nifedipine and removal of extracellular Ca2+. We conclude that, as in the carotid body type l cells, PC 12 cells and cortical neurons, increasing severity of hypoxia causes a proportional decrease in Ik, Em and increase of intracellular [Ca2+].
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