Role of KCNQ1 in the cell swelling-induced enhancement of the slowly activating delayed rectifier K+ current

Cell swelling enhances a slowly activating delayed rectifier K+ current (/(Ks)) in cardiac cells. This investigation was undertaken to determine which of the two structural units reconstituting the /(Ks) channel, KCNQ1 (KvLQT1) and KCNE1 (minK/IsK), plays a key role in the cell swelling-induced /(Ks) enhancement and to dissect a possible involvement of tyrosine phosphorylation therein. KCNQ1 was transiently expressed alone or together with KCNE1 in a heterologous mammalian cell line. Two distinct whole-cell membrane currents were separately observed during the exposure of transfected cells to various degrees of hyposmotic solutions. A hyposmotic challenge (0.7 times control osmolarity) resulted in about a twofold increase not only in the heteromeric KCNQ1/KCNE1, but also in the homomeric KCNQ1 channel currents. There was no significant difference in the incremental ratio of current amplitude in response to hyposmotic stress between the two KCNQ1-related currents, and the cells expressing the heteromeric channels swelled less than those with the homomeric channels or without the exogenous ones. The cell swelling-induced /(Ks) enhancement was not affected by a protein tyrosine kinase (PTK) inhibitor, by genistein (50 muM), or by an inhibitor of phosphotyrosine phosphatase (PTP), orthovanadate (500 muM), or a nonhydrolyzable ATP analogue, AMP-PNP (5 mM). Taken together, it is very likely that KCNQ1 might primarily participate in the /(Ks) enhancement by osmotic cell swelling. The obligatory dependence of the /(Ks) augmentation on PTK activity remained to be demonstrated, at least, in this expression system.