Lithium reversibly inhibits microtubule-based motility in sperm flagella

The sliding-tubule hypothesis of flagellar movement has strong experimental support, but our present knowledge of the mechanism by which this sliding is coordinated and converted into flagellar oscillation and bend propagation is quite limited. Among the few facts known are: (1) calcium has a role in regulating the asymmetry of flagellar waveform, (2) the initiation or activation of motility in spermatozoa from several species involves a cyclic AMP-dependent phosphorylation reaction, and (3) the conversion of tubule sliding to bending does not require the radial spokes or central tubules. Inhibitors are valuable tools for investigating mechanisms involved in cellular function, and we report here that Li+ in low concentrations reversibly inhibits the microtubule-based movement of reactivated sea urchin sperm flagella. The evidence indicates that the action of Li+ is directed primarily towards one or more regulatory sites through which Ca2+ modulates the asymmetry of flagellar waveform, rather than towards dynein ATPase itself. Lithium also appears to inhibit the sperm adenylate cyclase, but this action does not seem to be relevant to its inhibition of normal motility. Our findings indicate the need for considerable caution when using ATP analogues supplied as the Li+ salt.