Fendiline inhibits L-type calcium channels in guinea-pig ventricular myocytes: a whole-cell patch-clamp study.
1. Fendiline, a diphenylalkylamine type of antianginal drug, was examined for its effects on L-type calcium channels in guinea-pig ventricular myocytes by the whole-cell patch-clamp technique. 2. Fendiline (0.3-100 microM) applied extracellularly inhibited the calcium channel current (ICa) in a concentration- and time-dependent manner. The IC50 of fendiline was 17.0 +/- 2.43 microM and the Hill slope was 1.39 +/- 0.23. 3. Inhibition of ICa by fendiline appeared with an onset of less than 3 s. 4. Fendiline inhibited ICa at all the membrane potentials tested and shifted the current-voltage curve upwards. The overall calcium channel conductance (gCa) of the cell was reduced and conductance-voltage curve was shifted to the left in the presence of fendiline. 5. Isoprenaline (0.5-1 microM), a beta-adrenoceptor agonist, partially reversed the inhibitory effect of fendiline on ICa. 6. It is suggested that fendiline applied extracellularly blocks L-type calcium channels and reduces calcium channel conductance of the cell. The calcium channels thus inhibited are, nevertheless, still available for beta-adrenoceptor stimulation.
Tripathi
O
O
Institute of Medical Physics and Biophysics, Karl-Franzens University, School of Medicine, Graz, Austria.
Schreibmayer
W
W
Tritthart
H A
HA
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002794:Choline / Q000494:pharmacology; D003470:Culture Media; D004594:Electrophysiology; D005275:Fendiline / Q000494:pharmacology*; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D013779:Tetrodotoxin / Q000494:pharmacology
D002121:Calcium Channel Blockers; D003470:Culture Media; D013779:Tetrodotoxin; D007545:Isoproterenol; D002794:Choline; D005275:Fendiline