title: Role of Ca(2+)-sensitive K(+) channels in the remission phase of pulmonary hypertension in chronic obstructive pulmonary diseases.
abstract: 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 (BK(Ca)) in both CH-PAHT and N-RE phases. In the present study, we investigated the effects of both CH and N-RE on BK(Ca) 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 BK(Ca) 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 BK(Ca) blocker. The IbTx-sensitive whole-cell K(Ca) channel current was reduced in CH-PAHT and increased in N-RE rat PASMCs. The BK(Ca) 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 BK(Ca) alpha-subunit in CH, whereas no change at protein level was observed in the N-RE.
  
  
  CONCLUSIONS
  In rat PASMCs, CH and N-RE are associated with a down- and up-regulation of BK(Ca) activity, respectively, mainly due to modifications of its Ca(2+) sensitivity. This could explain the acute hypoxic pulmonary constriction and relaxation observed in CH and N-RE rats, respectively.
authors: INSERM (EMI 0356), Université Bordeaux 2, 146 rue Léo-Saignat, 33076, Bordeaux, France. sebastienbonnet@lpcr.u-bordeaux2.fr
authors: Sébastien
authors: S
authors: Bonnet
authors: Jean-Pierre
authors: JP
authors: Savineau
authors: Wilfrid
authors: W
authors: Barillot
authors: Eric
authors: E
authors: Dubuis
authors: Christophe
authors: C
authors: Vandier
authors: Pierre
authors: P
authors: Bonnet
mesh_terms: D000818:Animals; D015153:Blotting, Western / Q000379:methods; D002118:Calcium / Q000378:metabolism; D006976:Hypertension, Pulmonary / Q000378:metabolism / Q000503:physiopathology*; D000860:Hypoxia; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000503:physiopathology*; D018408:Patch-Clamp Techniques; D010455:Peptides / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D024681:Potassium Channels, Calcium-Activated / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D011651:Pulmonary Artery / Q000378:metabolism / Q000503:physiopathology*; D029424:Pulmonary Disease, Chronic Obstructive / Q000378:metabolism / Q000503:physiopathology*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014664:Vasodilation / Q000187:drug effects
chemical_list: D010455:Peptides; D026902:Potassium Channel Blockers; D024681:Potassium Channels, Calcium-Activated; D012333:RNA, Messenger; C064719:iberiotoxin; D002118:Calcium