Bovine adrenal zona fasciculata (AZF) cells express bTREK-1 background K ϩ channels that set the resting membrane potential. Whole-cell and single-channel patch-clamp recording were used to compare five Ca 2ϩ channel antagonists with respect to their potency as inhibitors of native bTREK-1 K ϩ channels. The dihydropyridine (DHP) Ca 2ϩ channel antagonists amlodipine and niguldipine potently and specifically inhibited bTREK-1 with IC 50 values of 0.43 and 0.75 M, respectively. The other Ca 2ϩ channel antagonists, including the DHP nifedipine, the diphenyldiperazine flunarizine, and the cannabinoid anandamide were less potent, with IC 50 values of 8.18, 2.48, and 5.07 M, respectively. Additional studies with the highly prescribed antihypertensive amlodipine showed that inhibition of bTREK-1 by this agent was voltage-independent and specific. At concentrations that produced near complete block of bTREK-1, amlodipine inhibited voltage-gated K v 1.4 K ϩ and T-type Ca 2ϩ