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

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Sci. Signal.  18 Aug 2015:
Vol. 8, Issue 390, pp. ra83
DOI: 10.1126/scisignal.aac5128

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Pressured to the surface

Pressure in arteries depolarizes vascular smooth muscle cells, activating voltage-dependent channels. Activation of voltage-dependent calcium (Cav) channels stimulates vasoconstriction; activation of voltage-dependent potassium (Kv) channels mediates vasodilation. Blood pressure and tissue perfusion are largely controlled by the constriction of resistance-sized arteries. Kidd et al. found that intravascular pressure also increased the amount of a specific Kv channel protein at the surface of myocytes of resistance-sized mesenteric arteries, which enhanced this vasoconstriction-opposing current in intact blood vessels. Thus, pressure-induced depolarization not only activates surface Kv channels but also selectively increases the abundance of specific Kv proteins to control blood flow and pressure.


Voltage-dependent potassium (Kv) channels are present in various cell types, including smooth muscle 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 voltage-dependent Ca2+ (Cav) channels that results in vasoconstriction and also K+ efflux through Kv channels that oppose vasoconstriction. We hypothesized that pressure-induced depolarization may not only increase the open probability of plasma membrane–resident Kv channels but also increase the abundance of these channels at the surface of arterial myocytes to limit vasoconstriction. We found that Kv1.5 and Kv2.1 proteins were 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 in myocytes 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–induced membrane depolarization selectively increased Kv1.5 surface abundance to increase Kv currents in arterial myocytes, which would limit vasoconstriction.

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