KV2.1 channels mediate hypoxic inhibition of IKV in native pulmonary arterial smooth muscle cells of the rat

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Abstract
Objective: To determine whether, in native pulmonary arterial smooth muscle cells (PASMC), KV2.1 delayed-rectifying K+ channels are central to the process of hypoxic pulmonary vasoconstriction. Methods: In this study, we tested for the presence of KV2.1 channel transcripts in rat small pulmonary arteries using RT-PCR, and for the protein itself using immunolocalisation. The contribution of KV2.1 channels to whole-cell KV currents ( I KV) and their role in hypoxic inhibition of I KV in native PASMC was investigated utilising patch-clamp recordings. Results: KV2.1 mRNA expression and AbKV2.1 (anti-KV2.1 antibody) protein immunoreactivity were both present in small pulmonary arteries. Dialysis of PASMC with AbKV2.1 significantly attenuated I KV by 67% at +50 mV. Hypoxia (∼20–30 mmHg) inhibited I KV by ∼70% at +50 mV. Ablation of currents associated with KV2.1 using AbKV2.1 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 KV2.1 channel subunits exist within small pulmonary arteries and conduct a significant part of I KV within native PASMC. Furthermore, application of AbKV2.1 abolishes hypoxic inhibition of I KV in native PASMC suggesting that KV2.1 channels play a pivotal role in mediating hypoxic pulmonary vasoconstriction.