Membrane depolarization activates BK channels through ROCK-mediated β1 subunit surface trafficking to limit vasoconstriction

See allHide authors and affiliations

Science Signaling  09 May 2017:
Vol. 10, Issue 478, eaah5417
DOI: 10.1126/scisignal.aah5417

This article has a correction. Please see:

Trafficking patterns for vasodilation

Constriction of the small arteries that regulate regional organ blood flow occurs due to membrane depolarization of arterial myocytes, which stimulates voltage-dependent Ca2+ channels that mediate the influx of Ca2+ ions. Dilation of these blood vessels from the constricted state can occur due to BK channels, which are activated by Ca2+, partially reversing the membrane depolarization of arterial myocytes. Leo et al. found that membrane depolarization triggered a signaling pathway that ensured the activation of BK channels. Ca2+ influx through voltage-dependent Ca2+ channels activated kinases that increased the trafficking of the β1 auxiliary subunit of the BK channel to the plasma membrane, where it bound to the pore-forming subunit to increase its sensitivity to Ca2+. Thus, BK channels are activated in depolarized arterial myocytes not only because of direct stimulation by Ca2+, but also because of the increased plasma membrane abundance of the subunit that determines their sensitivity to Ca2+.


Membrane depolarization of smooth muscle cells (myocytes) in the small arteries that regulate regional organ blood flow leads to vasoconstriction. Membrane depolarization also activates large-conductance calcium (Ca2+)–activated potassium (BK) channels, which limits Ca2+ channel activity that promotes vasoconstriction, thus leading to vasodilation. We showed that in human and rat arterial myocytes, membrane depolarization rapidly increased the cell surface abundance of auxiliary BK β1 subunits but not that of the pore-forming BKα channels. Membrane depolarization stimulated voltage-dependent Ca2+ channels, leading to Ca2+ influx and the activation of Rho kinase (ROCK) 1 and 2. ROCK1/2-mediated activation of Rab11A promoted the delivery of β1 subunits to the plasma membrane by Rab11A-positive recycling endosomes. These additional β1 subunits associated with BKα channels already at the plasma membrane, leading to an increase in apparent Ca2+ sensitivity and activation of the channels in pressurized arterial myocytes and vasodilation. Thus, membrane depolarization activates BK channels through stimulation of ROCK- and Rab11A-dependent trafficking of β1 subunits to the surface of arterial myocytes.

View Full Text

Stay Connected to Science Signaling