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| Title: | DIFFERENTIAL EFFECTS OF MEFENAMIC ACID ON CARDIAC IKs AND THE KCNQ1/KCNE1 CHANNELS | |
| DOI No: | 10.1142/9789812702234_0072 | |
| Source: | ADVANCES IN ELECTROCARDIOLOGY 2004 (pp 271-273) | |
| Author(s): | FUTOSHI TOYODA
Department of Physiology, Shiga University of Medical Science, Seta-Tsukinowacho, Otsu, Shiga 520-2192, Japan WEI-GUANG DING Department of Physiology, Shiga University of Medical Science, Seta-Tsukinowacho, Otsu, Shiga 520-2192, Japan ZANKOV DIMITAR Department of Physiology, Shiga University of Medical Science, Seta-Tsukinowacho, Otsu, Shiga 520-2192, Japan HIROSHI MATSUURA Department of Physiology, Shiga University of Medical Science, Seta-Tsukinowacho, Otsu, Shiga 520-2192, Japan |
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| Abstract: | Mefenamic acid is a nonsteroidal anti-inflammatory agent and affects a variety of ion channels. In the present study, we investigated the effects of mefenamic acid on native IKs channels in guinea-pig atrial cells and heteromeric KCNQ1/KCNE1 channels expressed in COS-7 cells, using the whole-cell patch-clamp technique. Both IKs and KCNQ1/KCNE1 currents were identified as the chromanol 293B-sensitive current. The KCNQ1/KCNE1 channel exhibited the voltage- and time-dependent activation during depolarizing voltage-clamp steps applied from a holding potential of -80 mV. Bath application of 0.1 mM mefenamic acid markedly increased the amplitude of instantaneous outward current but decreased the time-dependent current of the KCNQ1/KCNE1 channel upon depolarizations. These changes in current properties in the presence of mefenamic acid were facilitated during repetitive depolarizations. Mefenamic acid thus appears to stabilize the KCNQ1/KCNE1 channel in its open state; the channels once activated by depolarization hardly deactivate upon repolarization. In contrast, native IKs was scarcely affected by mefenamic acid at concentrations up to 1 mM, with the exception that the deactivation kinetics was slightly slowed, which suggests that mefenamic acid does not appreciably affect IKs, in vivo. We conclude that native IKs and the reconstituted KCNQ1/KCNE1 channels represent a marked differential sensitivity to mefenamic acid. | |
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