© 2002 by European Society of Cardiology
Copyright © 2002, European Society of Cardiology
KV2.1 channels mediate hypoxic inhibition of IKV in native pulmonary arterial smooth muscle cells of the rat
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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