The role of ion channels in hypoxic pulmonary vasoconstriction.

VA Medical Center, 1 Veterans Drive, 111C, Minneapolis, MN, 55417, USA.
Advances in experimental medicine and biology (Impact Factor: 1.83). 01/2010; 661:3-14. DOI: 10.1007/978-1-60761-500-2_1
Source: PubMed

ABSTRACT Hypoxic pulmonary vasoconstriction (HPV) is an important mechanism by which localized flow of blood in small resistance pulmonary arteries is matched to alveolar ventilation. This chapter discusses the role of several potassium and calcium channels in HPV, both in enhancing calcium influx into smooth muscle cells (SMCs) and in stimulating the release of calcium from the sarcoplasmic reticulum, thus increasing cytosolic calcium. The increase in calcium sensitivity caused by hypoxia is reviewed in Chapter 19. Particular attention is paid to the activity of the L-type calcium channels which increase calcium influx as a result of membrane depolarization and also increase calcium influx at any given membrane potential in response to hypoxia. In addition, activation of the L-type calcium channel may, in the absence of any calcium influx, cause calcium release from the sarcoplasmic reticulum. Many of these mechanisms have been reported to be involved in both HPV and in normoxic contraction of the ductus arteriosus.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Pulmonary arterial hypertension (PAH) is associated with sustained vasoconstriction, profound structural remodeling of vasculatures and alterations in Ca(2+) homeostasis in arterial smooth muscle cells (SMCs), while the underlying mechanisms are still elusive. By regulating the expression of proteins, microRNAs (miRNAs) are known to play an important role in cell fates including differentiation, apoptosis and proliferation, and may be involved in the development of PAH. Based on our previous study, hypoxia produced a significant increase of the miR-190 level in the pulmonary artery (PA), here, we used synthetic miR-190 to mimic the increase in hypoxic conditions and showed evidence for the effects of miR-190 on pulmonary arterial vasoconstriction and Ca(2+) influx in arterial SMCs. Synthetic miR-190 remarkably enhanced the vasoconstriction responses to phenylephrine (PE) and KCl. The voltage-gated K(+) channel subfamily member, Kcnq5, mRNA was shown to be a target for miR-190. Meanwhile, miR-190 antisense oligos can partially reverse the effects of miR-190 on PASMCs and PAs. Therefore, these results suggest that miR-190 appears to be a positive regulator of Ca(2+) influx, and play an important role in hypoxic pulmonary vascular constriction. J. Cell. Biochem. 9999: XX-XX, 2014. © 2013 Wiley Periodicals, Inc.
    Journal of Cellular Biochemistry 01/2014; · 3.06 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Reduced mitochondrial oxidative phosphorylation, via activation of adenylate kinase and the resulting exponential rise in the cellular AMP/ATP ratio, appears to be a critical factor underlying O₂ sensing in many chemoreceptive tissues in mammals. The elevated AMP/ATP ratio, in turn, activates key enzymes that are involved in physiologic adjustments that tend to balance ATP supply and demand. An example is the conversion of AMP to adenosine via 5'-nucleotidase and the resulting activation of adenosine A(₂A) receptors, which are involved in acute oxygen sensing by both carotid bodies and the brain. In fetal sheep, A(₂A) receptors associated with carotid bodies trigger hypoxic cardiovascular chemoreflexes, while central A(₂A) receptors mediate hypoxic inhibition of breathing and rapid eye movements. A(₂A) receptors are also involved in hypoxic regulation of fetal endocrine systems, metabolism, and vascular tone. In developing lambs, A(₂A) receptors play virtually no role in O₂ sensing by the carotid bodies, but brain A(₂A) receptors remain critically involved in the roll-off ventilatory response to hypoxia. In adult mammals, A(₂A) receptors have been implicated in O₂ sensing by carotid glomus cells, while central A(₂A) receptors likely blunt hypoxic hyperventilation. In conclusion, A(₂A) receptors are crucially involved in the transduction mechanisms of O₂ sensing in fetal carotid bodies and brains. Postnatally, central A(₂A) receptors remain key mediators of hypoxic respiratory depression, but they are less critical for O₂ sensing in carotid chemoreceptors, particularly in developing lambs.
    AJP Regulatory Integrative and Comparative Physiology 06/2011; 301(3):R601-22. · 3.28 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The influence of hypoxia on the activity of voltage-gated potassium channel in pulmonary artery smooth muscle cells (PASMCs) of rats and its roles in the pathogenesis of chronic pulmonary heart disease were investigated. Eighty male Sprague-Dawley rats were randomly allocated into control group (n=10), acute hypoxic group (n=10), and chronic hypoxic groups (n=60). The chronic hypoxic groups were randomly divided into 6 subgroups (n=10 each) according to the chronic hypoxic periods. The rats in the control group were kept in room air and those in acute hypoxic group in hypoxia environmental chamber for 8 h. The rats in chronic hypoxic subgroups were kept in hypoxia environmental chamber for 8 h per day for 5, 10, 15, 20, 25, and 30 days, respectively. The mean pulmonary arterial pressure (mPAP), right ventricular hypertrophy index (RVHI), and the current of voltage-gated potassium channel (I K) in PASMCs were measured. Results showed that both acute and chronic hypoxia could decrease the I K in PASMCs of rats and the I-V relationship downward shifted to the right. And the peak I K density at +60mV decreased with prolongation of hypoxia exposure. No significant difference was noted in the density of I K (at +60 mV) and I-V relationship between control group and chronic hypoxic subgroup exposed to hypoxia for 5 days (P>0.05), but there was a significant difference between control group and chronic hypoxic subgroup exposed to hypoxia for 10 days (P<0.05). Significant differences were noted in the I K density (at +60 mV) and I-V relationships between control group and chronic hypoxic subgroups exposed to hypoxia for 20 days and 30 days (P<0.01). Compared with control rats, the mPAP and RVHI were significantly increased after chronic exposure to hypoxia for 10 days (P<0.05), which were further increased with prolongation of hypoxia exposure, and there were significant differences between control group and chronic hypoxic subgroups exposed to hypoxia for 20 days and 30 days (P<0.01). Both the mPAP and the RVHI were negatively correlated with the density of I K (r=-0.89769 and -0.94476, respectively, both P<0.01). It is concluded that exposure to hypoxia may cause decreased activity of voltage-gated potassium channel, leading to hypoxia pulmonary vasoconstriction (HPV). Sustained HPV may result in chronic pulmonary hypertension, even chronic pulmonary heart disease, contributing to the pathogenesis of chronic pulmonary heart disease.
    Journal of Huazhong University of Science and Technology 10/2013; 33(5):644-9. · 0.58 Impact Factor


Available from