Voltage and pH dependent block of cloned N-type Ca2+ channels by amlodipine.
1. Two types of Ca2+ channel alpha1-subunits were co-expressed in Xenopus oocytes with the Ca2+ channel alpha2- and beta1-subunits. The Ba2+ current through the alpha1C alpha2beta and the alpha1B alpha2beta channels had electrophysiological and pharmacological properties of L- and N-type Ca2+ channels, respectively. 2. Amlodipine had a strong blocking action on both the L-type and N-type Ca2+ channels expressed in the oocyte. The potency of the amlodipine block on the N-type Ca2+ channel was comparable to that on the L-type Ca2+ channel. At -100 mV holding potential, the IC50 values for amlodipine block on the L-type and N-type Ca2+ channel were 2.4 and 5.8 microM, respectively. 3. The blocking action of amlodipine on the N-type Ca2+ channel was dependent on holding potential and extracellular pH, as has been observed with amlodipine block on the L-type Ca2+ channel. A depolarized holding potential and high pH enhanced the blocking action of amlodipine. 4. The time course of block development by amlodipine was similar for L-type and N-type Ca2+ channels. However, it was slower than the time course of block development by nifedipine for the L-type Ca2+ channel.
Furukawa
T
T
First Department of Internal Medicine, Teikyo University, Itabashi-ku, Tokyo, Japan.
Nukada
T
T
Suzuki
K
K
Fujita
Y
Y
Mori
Y
Y
Nishimura
M
M
Yamanaka
M
M
D017311:Amlodipine / Q000494:pharmacology*; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects* / Q000235:genetics; D003001:Cloning, Molecular; D006863:Hydrogen-Ion Concentration; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000235:genetics; D014981:Xenopus
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D011994:Recombinant Proteins; D017311:Amlodipine