Mefenamic acid as a novel activator of L-type voltage-dependent Ca 2+ channels in smooth muscle cells from pig proximal urethra

Abstract

The effects of mefenamic acid and Bay K 8644 on voltage-dependent nifedipine-sensitive inward Ba 2+ currents in pig urethral myocytes were investigated by use of conventional whole-cell configuration patch clamp. Mefenamic acid increased the peak amplitude of voltage-dependent nifedipine-sensitive inward Ba 2+ current without shifting the position of the current-voltage relationship. Mefenamic acid (300 μM) caused little shift in the activation curve although the voltage dependence of the steady-state inactivation was shifted to more positive potentials by 11 mV in the presence of mefenamic acid. Bay K 8644 (≥ 100 nM) enhanced voltage-dependent nifedipine-sensitive inward Ba 2+ currents in a concentration- and voltage-dependent manner, shifting the maximum of the current-voltage relationship by 10 mV in the hyperpolarizing direction. Bay K 8644 (1 μM) significantly shifted the voltage dependence of the activation curve to more negative potentials by approximately 9 mV although Bay K 8644 caused little shift in the steady-state inactivation curve. These results indicate that mefenamic acid increased voltage-dependent nifedipine-sensitive inward Ba 2+ currents through the activation of L-type Ca 2+ channels with different kinetics from those of Bay K 8644 in pig urethral myocytes. © 2005 Nature Publishing Group. All rights reserved.