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Emerging Concepts in Ion Channel Biophysics
Poster Abstracts
70
14-POS
Board 14
Regulation of Vascular Kv7 Channels by Gq- and Gs- Coupled Receptor Signaling
Kenneth L. Byron
1
, Leanne L. Cribbs
2
, Lyubov I. Brueggemann
1
.
1
Loyola University Chicago, Maywood, IL, USA,
2
Loyola University Chicago, Maywood, IL,
USA.
Kv7 (KCNQ) potassium channels are important regulators of membrane voltage in excitable
cells. We previously found that Kv7.4 and Kv7.5 α-subunits assemble to form the predominant
functional channels in mesenteric artery myocytes. These vascular Kv7 channels are regulated by
G-protein coupled receptors. Arginine-vasopressin (AVP) activates G
q
-coupled V
1a
receptors and
suppresses the activity of vascular Kv7 channels in a protein kinase C (PKC) –dependent
manner. Conversely, activity of the same vascular Kv7 channels is enhanced upon activation of
β-adrenergic G
s
- coupled receptors, in a protein kinase A (PKA)- dependent manner. The
responsiveness of vascular smooth muscle Kv7 channel subunits to both G
q
-coupled V
1a
receptor
activation and G
s
-coupled β-adrenergic receptor activation follows the order of Kv7.5>
Kv7.4/Kv7.5>> Kv7.4. We found that G
q
- and G
s
-coupled receptor-mediated regulation of
vascular Kv7 channels was associated with phosphorylation of Kv7.5 channel subunits. When
G
q
-coupled V
1a
receptors and G
s
-coupled β-adrenergic receptors were activated in sequence, G
s
-
coupled regulation dominated over G
q
-coupled regulation of endogenous Kv7.5 channels in A7r5
vascular smooth muscle cells. Activity of all known Kv7 channels critically depends on the
presence of a minor membrane phospholipid, phosphatidylinositol 4,5-bisphosphate (PIP
2
). We
hypothesize that the opposing effects of PKC activation and PKA activation are due to
differential phosphorylation of Kv7.5 α-subunits, which alters the affinity of the channels for
PIP
2
. In recent studies we found that activators of PKA opposed the time-dependent loss of
Kv7.5 currents in response to treatments that reduce PIP
2
levels. New evidence suggests that
specific serine residues present in Kv7.5, but not Kv7.4, and which are phosphorylated following
PKA activation, may account for this effect. Overall, we propose that complex regulation of
vascular Kv7 channels by G-protein coupled receptors depends on Kv7.5 channel α-subunit
phosphorylation and modulation of their affinity to PIP
2
.