Nonenzymatically oxidized arachidonic acid regulates T-type Ca2+ currents in mouse spermatogenic cells

During spermatogenesis, fatty acids play an important role both as structural components and messengers that trigger male germ cell line differentiation. The spontaneous oxidation of fatty acids causes a decrease in mammalian fertility. Here, we examine the effects of nonenzymatically oxidized arachidonic acid (AA(ox)) on mouse spermatogenic T-type Ca2+ currents (I-CaT) due to their physiological relevance during spermatogenesis. AA(ox) is 25-fold more potent than AA at inhibiting I-CaT and it left shifts the I-V curve peak and both activation and steady-state inactivation curves. In addition, I-CaT deactivation kinetics and their recovery from inactivation are slower in the presence of AA(ox). Therefore, the fraction of inactivated Ca2+ channels is increased. AA(ox)-induced I-CaT inhibition could contribute to male infertility affecting Ca2+ regulation in spermatogenic cells.