Role of Ca(2+)-sensitive K(+) channels in the remission phase of pulmonary hypertension in chronic obstructive pulmonary diseases.

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.

CONCLUSION

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.