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

1 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. 2 Mefenamic acid increased the peak amplitude of voltage‐dependent nifedipine‐sensitive inward Ba 2+ current without shifting the position of the current–voltage relationship. 3 Mefenamic acid (300  μ M ) 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. 4 Bay K 8644 (100 n M ) 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. 5 Bay K 8644 (1  μ M ) 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. 6 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.British Journal of Pharmacology (2005) 144 , 919–925. doi: 10.1038/sj.bjp.0706051