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Objective: To determine whether, in native pulmonary arterial smooth muscle cells (PASMC), K(V)2.1 delayed-rectifying K(+) channels are central to the process of hypoxic pulmonary vasoconstriction., Methods: In this study, we tested for the presence of K(V)2.1 channel transcripts in rat small pulmonary arteries using RT-PCR, and for the protein itself using immunolocalisation. The contribution of K(V)2.1 channels to whole-cell K(V) currents (I(KV)) and their role in hypoxic inhibition of I(KV) in native PASMC was investigated utilising patch-clamp recordings., Results: K(V)2.1 mRNA expression and AbK(V)2.1 (anti-K(V)2.1 antibody) protein immunoreactivity were both present in small pulmonary arteries. Dialysis of PASMC with AbK(V)2.1 significantly attenuated I(KV) by 67% at +50 mV. Hypoxia ( approximately 20-30 mmHg) inhibited I(KV) by approximately 70% at +50 mV. Ablation of currents associated with K(V)2.1 using AbK(V)2.1 caused a marked reduction in the amplitude of I(KV). Hypoxia in the presence of the antibody did not affect the magnitude of I(KV)., Conclusions: These results indicate that K(V)2.1 channel subunits exist within small pulmonary arteries and conduct a significant part of I(KV) within native PASMC. Furthermore, application of AbK(V)2.1 abolishes hypoxic inhibition of I(KV) in native PASMC suggesting that K(V)2.1 channels play a pivotal role in mediating hypoxic pulmonary vasoconstriction.

In contrast to systemic arteries those of the pulmonary circulation constrict in response to hypoxia: a mechanism known as "hypoxic pulmonary vasoconstriction" (HPV). It is has been established that changes in alveolar oxygen tension are the primary stimulus for triggering HPV. The mechanisms underlying this unique response are unknown. Neither the role of the endothelium nor that of the smooth muscle of the pulmonary arteries in oxygen sensing has been elucidated, although both tissues may be involved. Evidence is accumulating to suggest that K+ channels located in the plasma membranes of pulmonary arterial smooth muscle cells may play an important role in oxygen sensing. This process may involve novel mechanisms of signal transduction and K+ channel regulation by charged intermediates, redox reactions or membrane-delimited factors.