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Hong, Z; Weir, EK; Nelson, DP; Olschewski, A.
Subacute hypoxia decreases voltage-activated potassium channel expression and function in pulmonary artery myocytes.
AMER J RESPIR CELL MOLEC BIOL 2004 31: 337-343. Doi: 10.1165/rcmb.2003-0386OC [OPEN ACCESS]
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Führende Autor*innen der Med Uni Graz
Olschewski Andrea
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Abstract:
Chronic hypoxia results in both structural changes in the pulmonary artery and a sustained increase in pulmonary vascular tone. This study investigated the effects of subacute moderate hypoxia on expression and function of potassium (K+) channels in rat pulmonary artery myocytes (PASMCs). The rats were kept at 0.67 atmospheres for 6, 12, or 24 h. We found that the expression of mRNA for voltage-activated K+ channels (Kv)1.2, Kv1.5, and Kv2.1 is reduced after less than 24 h of this moderate hypoxia. K+ current (Ik) is significantly inhibited in PASMCs from rats hypoxic for 24 h, resting membrane potential is depolarized and cytosolic [Ca2+] is increased in these cells. In addition, antibodies to Kv1.2, Kv1.5, and Kv2.1 inhibit Ik, cause membrane depolarization and attenuate both hypoxia- and 4-AP-induced elevation in [Ca2+]i in PASMCs from normoxic rats but not from 24 h hypoxic rats. Subacute hypoxia does not completely remove the mRNA for Kv1.2, Kv1.5, and Kv2.1, but antibodies against these channels no longer alter Ik or cytosolic calcium, suggesting that subacute hypoxia may inactivate the channels as well as reduce expression. As the expression of mRNA for Kv1.2, Kv1.5, and Kv2.1 is sensitive to subacute hypoxia and decreased expression/function of these channels has physiologic effects on membrane potential and cytosolic calcium, it seems likely that these Kv channels may also be involved in the mechanism of high-altitude pulmonary edema and possibly in the signaling of chronic hypoxic pulmonary hypertension.
Find related publications in this database (using NLM MeSH Indexing)
Altitude Sickness - genetics
Animals - genetics
Anoxia - genetics
Antibodies - pharmacology
Bronchoconstriction - genetics
Calcium - metabolism
Calcium Signaling - genetics
Cell Membrane - genetics
Delayed Rectifier Potassium Channels - genetics
Down-Regulation - genetics
Hypertension, Pulmonary - genetics
Kv1.2 Potassium Channel - genetics
Kv1.5 Potassium Channel - genetics
Male - genetics
Membrane Potentials - genetics
Muscle, Smooth, Vascular - cytology
Myocytes, Smooth Muscle - cytology
Potassium Channels - genetics
Potassium Channels, Voltage-Gated - genetics
Pulmonary Artery - cytology
Pulmonary Edema - genetics
RNA, Messenger - metabolism
Rats - metabolism
Rats, Sprague-Dawley - metabolism
Research Support, Non-U.S. Gov't - metabolism
Research Support, U.S. Gov't, P.H.S. - metabolism
Shab Potassium Channels - metabolism

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