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Pflügers Archiv - European Journal of Physiology

, Volume 463, Issue 2, pp 279–295 | Cite as

BKCa and KV channels limit conducted vasomotor responses in rat mesenteric terminal arterioles

  • Bjørn Olav Hald
  • Jens Christian Brings Jacobsen
  • Thomas Hartig Braunstein
  • Ryuji Inoue
  • Yushi Ito
  • Preben Graae Sørensen
  • Niels-Henrik Holstein-Rathlou
  • Lars Jørn JensenEmail author
Cardiovascular Physiology

Abstract

Intracellular Ca2+ signals underlying conducted vasoconstriction to local application of a brief depolarizing KCl stimulus was investigated in rat mesenteric terminal arterioles (<40 μm). Using a computer model of an arteriole segment comprised of coupled endothelial cells (EC) and vascular smooth muscle cells (VSMC) simulations of both membrane potential and intracellular [Ca2+] were performed. The “characteristic” length constant, λ, was approximated using a modified cable equation in both experiments and simulations. We hypothesized that K+ conductance in the arteriolar wall limit the electrotonic spread of a local depolarization along arterioles by current dissipation across the VSMC plasma membrane. Thus, we anticipated an increased λ by inhibition of voltage-activated K+ channels. Application of the BKCa channel blocker iberiotoxin (100 nM) onto mesenteric arterioles in vitro and inhibition of BKCa channel current in silico increased λ by 34% and 32%, respectively. Similarly, inhibition of KV channels in vitro (4-aminopyridine, 1 mM) or in silico increased λ by 41% and 21%, respectively. Immunofluorescence microscopy demonstrated expression of BKCa, Kv1.5, Kv2.1, but not Kv1.2, in VSMCs of rat mesenteric terminal arterioles. Our results demonstrate that inhibition of voltage-activated K+ channels enhance vascular-conducted responses to local depolarization in terminal arterioles by increasing the membrane resistance of VSMCs. These data contribute to our understanding of how differential expression patterns of voltage-activated K+ channels may influence conducted vasoconstriction in small arteriolar networks. This finding is potentially relevant to understanding the compromised microcirculatory blood flow in systemic vascular diseases such as diabetes mellitus and hypertension.

Keywords

Calcium Terminal arteriole Conducted vasoconstriction Intercellular communication Electrotonic conduction KV channel BKCa channel Computer model Simulation 

Abbreviations

4-AP

4-Aminopyridine

IbTx

Iberiotoxin

EC

Endothelial cell

VCR

Vascular-conducted response

VSMC

Vascular smooth muscle cell

Notes

Acknowledgments

LJJ was the recipient of a postdoctoral fellowship from the Japan Society for the Promotion of Science (JSPS), and a part of his work was carried out at the Department of Pharmacology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. BOH was a recipient of a Ph.D. fellowship from the Faculty of Health Sciences, University of Copenhagen. The study received grants-in-aid from JSPS, The Danish Medical Research Council, The Lundbeck Foundation, The Danish Heart Foundation, The Novo Nordisk Foundation, and Fonden til Lægevidenskabens Fremme.

Supplementary material

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Fig. S1

Low resolution (JPEG 450 kb)

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Fig. S1 High resolution (TIFF 3,216 kb)
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ESM 2 (PDF 363 kb)

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Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Bjørn Olav Hald
    • 1
  • Jens Christian Brings Jacobsen
    • 1
  • Thomas Hartig Braunstein
    • 1
  • Ryuji Inoue
    • 2
  • Yushi Ito
    • 3
  • Preben Graae Sørensen
    • 4
  • Niels-Henrik Holstein-Rathlou
    • 1
  • Lars Jørn Jensen
    • 1
    • 5
    Email author
  1. 1.Department of Biomedical Sciences, Faculty of Health SciencesUniversity of CopenhagenCopenhagenDenmark
  2. 2.Department of PhysiologyFukuoka University Medical SchoolFukuokaJapan
  3. 3.Kumamoto Health Science UniversityKumamotoJapan
  4. 4.Department of Chemistry, Faculty of Natural SciencesUniversity of CopenhagenCopenhagenDenmark
  5. 5.Department of Basic Animal and Veterinary Sciences, Faculty of Life SciencesUniversity of CopenhagenFrederiksbergDenmark

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