Nervous control of ciliary beating by Cl-, Ca2+ and calmodulin in Tritonia diomedea

In vertebrates, motile cilia line airways, oviducts and ventricles. Invertebrate cilia often control feeding, swimming and crawling, or gliding. Yet control and coordination of ciliary beating remains poorly understood. Evidence from the nudibranch mollusc, Tritonia diomedea, suggests that locomotory ciliated epithelial cells may be under direct electrical control. Here we report that depolarization of ciliated pedal epithelial (CPE) cells increases ciliary beating frequency (CBF), and elicits CBF increases similar to those caused by dopamine and the neuropeptide, TPep-NLS. Further, four CBF stimulants ( zero external Cl-, depolarization, dopamine and TPep-NLS) depend on a common mode of action, viz. Ca2+ influx, possibly through voltage-gated Ca2+ channels, and can be blocked by nifedipine. Ca2+ influx alone, however, does not provide all the internal Ca2+ necessary for CBF change. Ryanodine receptor (RyR) channel-gated internal stores are also necessary for CBF excitation. Caffeine can stimulate CBF and is sensitive to the presence of the RyR blocker dantrolene. Dantrolene also reduces CBF excitation induced by dopamine and TPep-NLS. Finally, W-7 and calmidazolium both block CBF excitation by caffeine and dopamine, and W-7 is effective at blocking TPep-NLS excitation. The effects of calmidazolium and W-7 suggest a role for Ca2+-calmodulin in regulating CBF, either directly or via Ca2+-calmodulin dependent kinases or phosphodiesterases. From these results we hypothesize dopamine and TPep-NLS induce depolarization-driven Ca2+ influx and Ca2+ release from internal stores that activates Ca2+-calmodulin, thereby increasing CBF.