Accordingly, in the second part of the article, we will review the potential roles of purinergic P2X7 receptors along with hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, M-type K+ (KCNQ) channels, TWIK-related K+ channels (TREK) and Ca+2 channels in the pathophysiology of depression, dysfunction of which are also implicated in migraine. The gene discussed is KCNK2; the disease is major depressive disorder.