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Cardiovascular Research 2003 60(2):326-336; doi:10.1016/S0008-6363(03)00527-3
© 2003 by European Society of Cardiology
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Copyright © 2003, European Society of Cardiology

Role of Ca2+-sensitive K+ channels in the remission phase of pulmonary hypertension in chronic obstructive pulmonary diseases

Sébastien Bonnet*,a, Jean-Pierre Savineaua, Wilfrid Barillotb, Eric Dubuisc, Christophe Vandierc and Pierre Bonnet*,c

aINSERM (EMI 0356), Université Bordeaux 2, 146 rue Léo-Saignat, 33076 Bordeaux, France
bINSERM U441, avenue du haut-Lévêque, 33600 Pessac, France
cLaboratoire de physiopathologie de la paroi artérielle (LABPART), Dept. de Physiologie, Faculté de Médecine, 2 bis Boulevard Tonnellé, 37032 Tours, Indre et Loire, France

*Corresponding authors. Tel.: +33-2-47-36-60-91; fax: +33-2-47-36-60-64. Email address: sebastien.bonnet{at}lpcr.u-bordeaux2.fr bonnet{at}med.univ-tours.fr

Objective: Clinically, the effect of chronic hypoxia (CH) in the pulmonary circulation alternates between phases of pulmonary artery hypertension (CH-PAHT) and normoxic normotensive remission (N-RE). Little information is available on the role of calcium-sensitive potassium channels (BKCa) in both CH-PAHT and N-RE phases. In the present study, we investigated the effects of both CH and N-RE on BKCa channels activity and their consequences on hypoxic pulmonary vasoconstriction (HPV). Methods: Using isolated ring preparation, the patch-clamp technique, RT-PCR and Western immunoblotting, we examined the role of the BKCa channel in normoxic, CH-PAHT and N-RE rat pulmonary artery smooth muscle cells (PASMCs). Results: In intrapulmonary arterial rings, acute hypoxia induced contraction in control vessels, relaxation in the N-RE rats, and had no effect in CH-PAHT. The hypoxia-induced relaxation in the N-RE rat pulmonary arteries was abolished by iberiotoxin (IbTx), a specific BKCa blocker. The IbTx-sensitive whole-cell KCa channel current was reduced in CH-PAHT and increased in N-RE rat PASMCs. The BKCa channel conductance and voltage sensitivity were not altered in CH and N-RE rat PASMCs, whereas its calcium sensitivity was decreased and increased in CH and N-RE rat PASMCs, respectively. Results of RT-PCR and Western blot analysis revealed a decrease in the mRNA and protein of the BKCa {alpha}-subunit in CH, whereas no change at protein level was observed in the N-RE. Conclusion: In rat PASMCs, CH and N-RE are associated with a down- and up-regulation of BKCa activity, respectively, mainly due to modifications of its Ca2+ sensitivity. This could explain the acute hypoxic pulmonary constriction and relaxation observed in CH and N-RE rats, respectively.

KEYWORDS Ion channels; K-channel; Pulmonary circulation; Smooth muscle; Single channel currents; Pulmonary artery; Chronic hypoxia; COPD; Hypertension; Ca2+-sensitive K+ channels

Abbreviations: CH-PAHT, chronic hypoxic pulmonary artery hypertension • N-RE, normoxic remission • CH, chronic hypoxia • PA, pulmonary artery • PASMCs, pulmonary artery smooth muscle cells • HPV, hypoxic pulmonary vasoconstriction

Time for primary review 23 days


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