The mechanism of action of cyanide on the oviductal cilia is not known. Acute cyanide toxicity occurs by irreversible inhibition of cytochrome oxidase aa3, which in turn shuts down oxygen utilization and ATP production. However, this is not the sole mechanism of action of cyanide on cells. Cyanide inhibits more than 40 enzymes and has numerous other effects on cells, many at the level of the plasma membrane. Cyanide also equilibrates rapidly across the plasma membrane of neuronal cells, then more slowly accumulates in the mitochondria and other membranous organelles. In our oviductal system, CBF and OPR were inhibited by KCN, but CBF recovered fairly rapidly to control values during washout. Since CBF always recovered to control levels, it is unlikely that inhibition was due to irreversible binding of cyanide to cytochrome oxidase accompanied by reduced ATP levels. It is more probable that cyanide was acting by another mechanism. In addition, the concentration of KCN (10 mM) usually used to deplete ATP in flagellated or ciliated cells is 200 times higher than the concentration of KCN (50 |jlM) that inhibited CBF and 666 times higher than the concentration (15 |iM) that inhibited OPR. These numbers indicate that proper functioning of the oviductal epithelium is sensitive to very low levels of cyanide, which appears to act by a mechanism other than ATP depletion. buy flovent inhaler
In cultured rat phenochromocytoma cells (PC 12 cells), cyanide elevates cytosolic calcium, apparently by mobilizing Ca2+ from intracellular compartments, and this leads to hyperpolarization of the membrane via activation of Ca2+-sensitive K+ channels. CBF is increased in preparations from vertebrate trachea and oviducts via a release of Ca2+ from intracellular stores; thus it is unlikely that KCN affected the oviduct by this mechanism. KCN may alter other membrane properties, and in neuronal cells lowers intracellular pH by interference with a Na+/H+ exchanger. If cytosolic acidification occurs in hamster oviduc-tal epithelial cells exposed to cyanide, CBF may be decreased by inhibition of dynein ATPase activity, which has an alkaline pH optimum.