TY - JOUR

T1 - Kv7.1 surface expression is regulated by epithelial cell polarization

AU - Andersen, Martin N

AU - Olesen, Søren-Peter

AU - Rasmussen, Hanne Borger

PY - 2011

Y1 - 2011

N2 - The potassium channel K(V)7.1 is expressed in the heart where it contributes to the repolarization of the cardiac action potential. In addition, K(V)7.1 is expressed in epithelial tissues where it plays a role in salt and water transport. Mutations in the kcnq1 gene can lead to long QT syndrome and deafness, and several mutations have been described as trafficking mutations. To learn more about the basic mechanisms that regulate K(V)7.1 surface expression, we have investigated the trafficking of K(V)7.1 during the polarization process of the epithelial cell line Madin-Darby Canine Kidney (MDCK) using a modified version of the classical calcium switch. We discovered that K(V)7.1 exhibits a very dynamic localization pattern during the calcium switch. When MDCK cells are kept in low calcium medium, K(V)7.1 is mainly observed at the plasma membrane. During the first hours of the switch, K(V)7.1 is removed from the plasma membrane and an intracellular accumulation in the endoplasmic reticulum (ER) is observed. The channel is retained in the ER until the establishment of the lateral membranes at which point K(V)7.1 is released from the ER and moves to the plasma membrane. Our data furthermore suggest that while the removal of K(V)7.1 from the cell surface and its accumulation in the ER could involve activation of protein kinase C, the subsequent release of K(V)7.1 from the ER depends on phosphoinositide 3-kinase (PI3K) activation. In conclusion, our results demonstrate that K(V)7.1 surface expression is regulated by signaling mechanisms involved in epithelial cell polarization in particular signaling cascades involving protein kinase C and PI3K.

AB - The potassium channel K(V)7.1 is expressed in the heart where it contributes to the repolarization of the cardiac action potential. In addition, K(V)7.1 is expressed in epithelial tissues where it plays a role in salt and water transport. Mutations in the kcnq1 gene can lead to long QT syndrome and deafness, and several mutations have been described as trafficking mutations. To learn more about the basic mechanisms that regulate K(V)7.1 surface expression, we have investigated the trafficking of K(V)7.1 during the polarization process of the epithelial cell line Madin-Darby Canine Kidney (MDCK) using a modified version of the classical calcium switch. We discovered that K(V)7.1 exhibits a very dynamic localization pattern during the calcium switch. When MDCK cells are kept in low calcium medium, K(V)7.1 is mainly observed at the plasma membrane. During the first hours of the switch, K(V)7.1 is removed from the plasma membrane and an intracellular accumulation in the endoplasmic reticulum (ER) is observed. The channel is retained in the ER until the establishment of the lateral membranes at which point K(V)7.1 is released from the ER and moves to the plasma membrane. Our data furthermore suggest that while the removal of K(V)7.1 from the cell surface and its accumulation in the ER could involve activation of protein kinase C, the subsequent release of K(V)7.1 from the ER depends on phosphoinositide 3-kinase (PI3K) activation. In conclusion, our results demonstrate that K(V)7.1 surface expression is regulated by signaling mechanisms involved in epithelial cell polarization in particular signaling cascades involving protein kinase C and PI3K.

KW - Adherens Junctions

KW - Animals

KW - Calcium

KW - Cell Line

KW - Cell Membrane

KW - Cell Polarity

KW - Desmosomes

KW - Dogs

KW - Endoplasmic Reticulum

KW - Enzyme Activation

KW - Epithelial Cells

KW - Humans

KW - KCNQ1 Potassium Channel

KW - Phosphatidylinositol 3-Kinases

KW - Protein Kinase C

KW - Protein Transport

KW - Signal Transduction

KW - Tight Junctions

U2 - 10.1152/ajpcell.00390.2010

DO - 10.1152/ajpcell.00390.2010

M3 - Journal article

C2 - 21228319

VL - 300

SP - C814-24

JO - American Journal of Physiology: Cell Physiology

JF - American Journal of Physiology: Cell Physiology

SN - 0363-6143

IS - 4

ER -