Non-enzymatically oxidized arachidonic acid regulates mouse spermatogenic cell T-type Ca2+ currents

Abstract

During spermatogenesis, phospholipids and fatty acids (FAs) play an important role both as structural components of spermatogenic cell plasma membranes and as molecular messengers that trigger the differentiation of the male germ cell line. However, spontaneous oxidation of plasma membrane phospholipids and FAs causes a decrease in mammalian fertility. In the present report, we examine the effects of non-enzymatically oxidized arachidonic acid (AAox) on mouse spermatogenic T-type Ca2+ currents (ICaT) due to their physiological relevance during spermatogenesis. AAox effects on the biophysical parameters of ICaT were significantly different from those previously reported for AA. AAox left shifted the I-V curve peak and both activation and steady-state inactivation curves. ICaT deactivation kinetics were slower in presence of AAox and the time for its recovery from inactivation increased significantly. Therefore, the fraction of inactivated Ca2+ channels of spermatogenic cells is increased at voltages where they are usually active. The inhibition of ICaT by AAox could contribute to the infertility phenotype and to the observed apoptotic state of spermatogenic cells induced by oxidized FAs.