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Cardiovascular Research 2002 55(2):349-360; doi:10.1016/S0008-6363(02)00411-X
© 2002 by European Society of Cardiology
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Copyright © 2002, European Society of Cardiology

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

Dayle S Hogga, Andrew R.L Daviesa, Gordon McMurrayb and Roland Z Kozlowskia,*

aDepartment of Pharmacology, School of Medical Sciences, University of Bristol, University Walk, Bristol BS8 1TD, UK
bUniversity Department of Pharmacology, Mansfield Road, Oxford OX1 3QT, UK

* Corresponding author. Tel.: +44-117-954-6875; fax: +44-117-925-2659 roland.kozlowski{at}bristol.ac.uk

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 (IKV) and their role in hypoxic inhibition of IKV 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 IKV by 67% at +50 mV. Hypoxia (~20–30 mmHg) inhibited IKV by ~70% at +50 mV. Ablation of currents associated with KV2.1 using AbKV2.1 caused a marked reduction in the amplitude of IKV. Hypoxia in the presence of the antibody did not affect the magnitude of IKV. Conclusions: These results indicate that KV2.1 channel subunits exist within small pulmonary arteries and conduct a significant part of IKV within native PASMC. Furthermore, application of AbKV2.1 abolishes hypoxic inhibition of IKV in native PASMC suggesting that KV2.1 channels play a pivotal role in mediating hypoxic pulmonary vasoconstriction.

KEYWORDS Arteries; Hypoxia/anoxia; K-channel; Myocytes; Pulmonary circulation


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