Intravascular pressure enhances the abundance of functional Kv1.5 channels at the surface of arterial smooth muscle cells

Research output: Contribution to journalArticle

Authors

External Institution(s)

  • University of Tennessee Health Science Center

Details

Original languageEnglish (US)
Pages (from-to)ra83
JournalScience signaling
Volume8
Issue number390
StatusPublished - Aug 18 2015
Peer-reviewedYes

Abstract

Voltage-dependent potassium(Kv) channels are present in various cell types, including smoothmuscle cells (myocytes) of resistance-sized arteries that control systemic blood pressure and regional organ blood flow. Intravascular pressure depolarizes arterial myocytes, stimulating calcium (Ca2+)influx through voltagedependent Ca2+(Cav) channels that results in vasoconstriction and also K+ efflux through Kv channels that oppose vasoconstriction. We hypothesized that pressure-induced depolarizationmay not only increase the open probability of plasmamembrane-residentKv channels but also increase the abundance of these channels at the surface of arterial myocytes to limit vasoconstriction.Wefound that Kv1.5 and Kv2.1 proteinswere abundant in the myocytes of resistance-sized mesenteric arteries. Kv1.5, but not Kv2.1, continuously recycled between the intracellular compartment and the plasma membrane in contractile arterial myocytes. Using ex vivo preparations of intact arteries, we showed that physiological intravascular pressure through membrane depolarization or membrane depolarization in the absence of pressure inhibited the degradation of internalized Kv1.5 and increased recycling of Kv1.5 to the plasma membrane. Accordingly, by stimulating the activity of Cav1.2, membrane depolarization increased whole-cell Kv1.5 current density inmyocytes and Kv1.5 channel activity in pressurized arteries. In contrast, the total amount and cell surface abundance of Kv2.1 were independent of intravascular pressure or membrane potential. Thus, our data indicate that intravascular pressure-inducedmembrane depolarization selectively increased Kv1.5 surface abundance to increase Kv currents in arterial myocytes, which would limit vasoconstriction.