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

1 Two types of Ca2+ channel alpha(1)-subunits were co-expressed in Xenopus oocytes with the Ca2+ channel alpha(2)- and beta(1)-subunits. The Ba2+ current through the alpha(1C)alpha(2) beta and the alpha(1B)alpha(2) beta 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 mu M, 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.