Identification of R(−)‐isomer of efonidipine as a selective blocker of T‐type Ca2+ channels
T Furukawa, R Miura, M Honda… - British journal of …, 2004 - Wiley Online Library
T Furukawa, R Miura, M Honda, N Kamiya, Y Mori, S Takeshita, T Isshiki, T Nukada
British journal of pharmacology, 2004•Wiley Online LibraryEfonidipine, a derivative of dihydropyridine Ca2+ antagonist, is known to block both L‐and T‐
type Ca2+ channels. It remains to be clarified, however, whether efonidipine affects other
voltage‐dependent Ca2+ channel subtypes such as N‐, P/Q‐and R‐types, and whether the
optical isomers of efonidipine have different selectivities in blocking these Ca2+ channels,
including L‐and T‐types. To address these issues, the effects of efonidipine and its R (−)‐
and S (+)‐isomers on these Ca2+ channel subtypes were examined electrophysiologically …
type Ca2+ channels. It remains to be clarified, however, whether efonidipine affects other
voltage‐dependent Ca2+ channel subtypes such as N‐, P/Q‐and R‐types, and whether the
optical isomers of efonidipine have different selectivities in blocking these Ca2+ channels,
including L‐and T‐types. To address these issues, the effects of efonidipine and its R (−)‐
and S (+)‐isomers on these Ca2+ channel subtypes were examined electrophysiologically …
- Efonidipine, a derivative of dihydropyridine Ca2+ antagonist, is known to block both L‐ and T‐type Ca2+ channels. It remains to be clarified, however, whether efonidipine affects other voltage‐dependent Ca2+ channel subtypes such as N‐, P/Q‐ and R‐types, and whether the optical isomers of efonidipine have different selectivities in blocking these Ca2+ channels, including L‐ and T‐types.
- To address these issues, the effects of efonidipine and its R(−)‐ and S(+)‐isomers on these Ca2+ channel subtypes were examined electrophysiologically in the expression systems using Xenopus oocytes and baby hamster kidney cells (BHK tk‐ts13).
- Efonidipine, a mixture of R(−)‐ and S(+)‐isomers, exerted blocking actions on L‐ and T‐types, but no effects on N‐, P/Q‐ and R‐type Ca2+ channels.
- The selective blocking actions on L‐ and T‐type channels were reproduced by the S(+)‐efonidipine isomer.
- By contrast, the R(−)‐efonidipine isomer preferentially blocked T‐type channels.
- The blocking actions of efonidipine and its enantiomers were dependent on holding potentials.
- These findings indicate that the R(−)‐isomer of efonidipine is a specific blocker of the T‐type Ca2+ channel.
British Journal of Pharmacology (2004) 143, 1050–1057. doi:10.1038/sj.bjp.0705944
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