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

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Bjørn Olav Hald, Jens Christian Brings Jacobsen, Thomas Hartig Braunstein, Ryuji Inoue, Yuski Ito, Preben Graae Sørensen, Niels-Henrik von Holstein-Rathlou, Lars Jørn Jensen

Intracellular Ca(2+) 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 [Ca(2+)] were performed. The "characteristic" length constant, ¿, 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 ¿ by inhibition of voltage-activated K(+) channels. Application of the BK(Ca) channel blocker iberiotoxin (100 nM) onto mesenteric arterioles in vitro and inhibition of BK(Ca) channel current in silico increased ¿ by 34% and 32%, respectively. Similarly, inhibition of K(V) channels in vitro (4-aminopyridine, 1 mM) or in silico increased ¿ by 41% and 21%, respectively. Immunofluorescence microscopy demonstrated expression of BK(Ca), 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.
OriginalsprogEngelsk
TidsskriftPflügers Archiv - European Journal of Physiology
Vol/bind463
Udgave nummer2
Sider (fra-til)279-295
Antal sider17
ISSN0031-6768
DOI
StatusUdgivet - 2012

    Forskningsområder

  • Det tidligere LIFE - Calcium, Terminal arterioe, Conducted vasoconstriction, Intercellula communication, Electronic conduction, Computer model, Simulation

ID: 35341455