Differential expression of KvLQT1 and its regulator IsK in mouse epithelia

KCNQ1 is the human gene responsible in most cases for the long QT syndrome, a genetic disorder characterized by anomalies in cardiac repolarization le ading to arrhythmias and sudden death. KCNQ1 encodes a pore-forming K+ chan nel subunit termed KvLQT1 which, in association with its regulatory beta -s ubunit IsK (also called minK), produces the slow component of the delayed-r ectifier cardiac K+ current. We used in situ hybridization to localize KvLQ T1 and IsK mRNAs in various tissues from adult mice. We showed that KvLQT1 mRNA expression is widely distributed in epithelial tissues, in the absence (small intestine, lung, liver, thymus) or presence (kidney, stomach, exocr ine pancreas) of its regulator IsK. In the kidney and the stomach, however, the expression patterns of KvLQT1 and IsK do not coincide. In many tissues , in situ data obtained with the IsK probe coincide with beta -galactosidas e expression in IsK-deficient mice in which the bacterial lacZ gene has bee n substituted for the IsK coding region. Because expression of KvLQT1 in th e presence or absence of its regulator generates a K+ current with differen t biophysical characteristics, the role of KvLQT1 in epithelial cells may v ary depending on the expression of its regulator IsK. The high level of KvL QT1 expression in epithelial tissues is consistent with its potential role in K+ secretion and recycling, in maintaining the resting potential, and in regulating Cl- secretion and/or Na+ absorption.