Characterization of Ca2+ current inhibition by cilnidipine using a beta-subunit antisense oligonucleotide.
The dihydropyridine cilnidipine has been reported to induce a fast decay of the L-type Ca(2+) current, an effect distinct from the modulation of voltage-dependent inactivation. We performed a whole-cell patch-clamp study using A7r5 cells to analyse the changes in current decay induced by two structurally related dihydropyridines after the amount of the beta-subunit mRNA has been decreased by the antisense oligonucleotide. The Ba(2+) current underwent a single exponential decay indicating voltage-dependent inactivation. The tau value was greater in the antisense group than in the sense and nonsense groups. Equipotent doses of cilnidipine and nimodipine decreased the tau value, while only cilnidipine created an additional component with a smaller tau value (tau(cil): 35 ms) that showed voltage-independence. Treatment with antisense failed to alter this component (tau(cil): 38 ms). These results suggest that cilnidipine specifically exerts a second type of blocking action on L-type Ca(2+) channels that is not dependent on the beta-subunit.
Uchida
Ryuji
R
Department of Oral and Maxillofacial Surgery, Fukuoka Dental College, 2-15-1 Tamura, Sawara-ku, 814-0193, Fukuoka, Japan.
Yamazaki
Jun
J
Kitamura
Kenji
K
D000818:Animals; D001464:Barium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000187:drug effects* / Q000502:physiology; D002460:Cell Line; D004095:Dihydropyridines / Q000494:pharmacology*; D007150:Immunohistochemistry; D015640:Ion Channel Gating; D009553:Nimodipine / Q000494:pharmacology; D016376:Oligonucleotides, Antisense / Q000235:genetics / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D021122:Protein Subunits / Q000235:genetics / Q000502:physiology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats
D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D004095:Dihydropyridines; D016376:Oligonucleotides, Antisense; D021122:Protein Subunits; D012333:RNA, Messenger; D001464:Barium; D009553:Nimodipine; C065927:cilnidipine