Abstract
The present study was designed to examine the effects of the nonsteroidal anti-inflammatory agent mefenamic acid on the native slowly activating delayed rectifier K+ current (IKs) and heterologously expressed KCNQ1/KCNE1 channels, the molecular constituents believed to underlie cardiac IKs. IKs in guinea-pig cardiac myocytes and KCNQ1/KCNE1 channel heterologously expressed in COS-7 cells were recorded using whole-cell patch-clamp method. Bath application of mefenamic acid (0.1 mM) gradually increased the amplitude of outward current jump but decreased the magnitudes of both the time-dependent developing current and deactivating tail current in the KCNQ1/KCNE1 channels during repetitively depolarization from a holding potential of –80 mV to various test potentials. These changes in the outward currents were totally sensitive to the IKs blocker chromanol 293B (100 μM). Thus, the KCNQ1/KCNE1 channels appear to be stabilized in an open state in the presence of mefenamic acid; the channel that is once activated by depolarization hardly deactivates upon repolarization. In contrast, mefenamic acid at the same concentration (0.1 mM) hardly affected the properties of native IKs with the exception that the deactivation kinetics was minimally slowed, consistent with the finding that mefenamic acid does not appreciably affect IKs in vivo. Thus, the present study confirms the presence of a marked differential sensitivity of native IKs and heterologously expressed KCNQ1/KCNE1 channel to mefenamic acid. [Jpn J Physiol 55 Suppl:S135 (2005)]
