Voltage and pH dependent block of cloned N-type Ca2+ channels by amlodipine

Abstract

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.