10-17diagaram ilustrating the idea that active sliding in a straight section of a flagellum on produces passive bending in opposite directions

in adjancent inactive regions. If passive bending activates the sliding mechanism (B) the sequence of alternating straight and curved regions will propagate along the axoneme (C) see text and figure 10-18 Relative sliding of the tubules it will be apparent that active sliding within one section of the axoneme will produce passive bending in opposite directions of the inactive section either side of the actively sliding section ( figure 10-17B) longitudinal propagation of activity along the axoneme can be explained if it is assumed that the bending of an inactive region stimulates it to become active (figure 10-17). Sliding forces produced by chemomechanical transduction in the active region will be transferred longitudinally to adjencent inactive regions, causing these to bend passively. The passive bending initianted by nearby active sliding initiates along the length of the axoneme. A mathematical computer simulation of movement patterns that closely resemble real flagellar movement (figure 10-18) sentitivity to mechanical strain is seen in the giant cilium found on the gill filament clams . this cilium ( aktucally a coselly packed bundle of very long individual cilia) remains poised indenfinitely et the end or its effective stroke under certain ionic condition (figure 10-19A) if then given a small passive displacement of active bending (figure 10-19D-G). intracelluler electricall recordings show no potential changes across ulus or the active mechanical reponse. Appently the mechanical stimulus acts directly on the mechanism responsible for active sliding. Evidence that ATPase activity is stimulated by mechanical forces associated with flagellar movement was obtained by slowing the frequency movement of glycerinated sperm tails by increasing the viscosity of the medium in which they were suspended this procendure produced a reduction in ATP hydrolysis depends on the frequency with which inactive regions are stimulated by region undergoing active bending a relation between passive tension production of in which ATPase activity and tension production of the cross bridges are stimulated by externally applied tension 10-18 propagation of alternating linier and bent regionsof exoneme along spem-tail flagellumsmall arrows show proposed active straight segments. This

countersliding of axoneural tubules in active straight segments this countersliding is believed of produce passive bending of the inactive neighboring segment. 10-19 mecanical activation of the glant cilium of the clam. A crystal driven microntylus is used to give the stationary cilium of abrupt displacement initiates an entire beat cycle (B-G) . (thum1968) Coordination of ciliary movement That question of control and coordination of movement to be considered here exist at three pricipall lavels first how is the beat initated and the beating frequency regulated? Second what couse in the individual cilia of a population to beat whith a timing that produces metacronal wavest that sweep steadily and peatedly over the ciliary field (figure 10-8) third how are the cilia of protozoa and certain metazoan epthelia controlled so as to undergo changes in the Spatial organization of the beat, most evident as a change in the direction of the power stroke and in the direction of the metachronal waves? SPONTANELTY AND BEATING FREQUENCY cilia and flagella exhibid endogenous rhythmicity. The organelller can beat or treatment whit detergents spontaneously apther isolation from a cell and they will beat afther extraction of the cell membrane and cytoplasmic metabolites glycerination (box9.1) I provided whit an external supply of ATP and essential ions. In certain speciest the flagellum continues to beat when it is severed near the base ang separated from the basal body (figure 10-20)it must be concluded that in the least some species, in the beat can originate in the shaft itself. The cilia of certain vertebrate epithelia (e.g frog 10-20 flagellar beat is severed from the cell body by a laser beam the flagellum continousto beat several cyclesuntil its ATP is exhausted (Goldstein et al 1970) 10-21 method of studying the neural control of ciliary beating. Electrical stimulation of the nerve that innervales the gils of the mussel mytilus stops the ciliary beat (A) THE exsperimental appratus a steadily moving strip of film travels past a slit while of the image of the metacronal waves of the beating ciliamoves along the longitudinal axis of

the slit (B) the movement produces a diagonal petterm on the film . alterationsin the activity of the colia interrupt this patten . ( C) records showing the stoppage of the beat of cilia in response to nerve stimulation ( takahashi and murakami, 1968). Palate increase their frequency of beating in respose to Ach and sliw down in response to epinephirene. They also increase beating frequency when nerves that release Ach in the tissue are stimulated. Brief electrical stimulation of the nerve innervating the ciliated gills of the mussel mytilus results in a transient cessation of ciliary activity (figure 10-21) this is presumed to result from the action of a transmitter substance released by the nerve terminals the same arrents of beating can be produced by experimental procedures that cause a rise in intracellular Ca in the ciliated cells of the gill. Thus, it has been postulated that the arresting action of the neurotransmitter is mediated by a rise in intracellular Ca the neurotransmitter serotonin has the opposite effect accelerating the cilia of clam and mussel gills and thus mimicking the excitatory effect of stimulating the branchial nerve. CILLIARY REVERSAL Most epithelial cilia beat in a fixed direction but the cilia of protozoa and of the epithelium of tunicate larvae can alter the direction of the power stroke. The most exsitensive investigations of cilliary reversal 10-22 orien tation of the metacronal wavest as a function of membrane potential the ciliate oplina immersed in various different potentials . the concentrations of KCL to set the membrane to potentials were recorderd with a microelectrode and the

orientation of metacronal wavest ( angle) a was plotted against the membrane potential (A) the more depolarized the membrane, the more anteriolly directed are the waves the different symbol in the graph refer to different specimen.(B) direction kinosita 1954) Have been made on ciliated protozoa there is an intimate relation between change in the direction of ciliary beat and changes in the direction of metacronal waves. A shift in the direction of the effective stroke is accompanied by similar shift in the direction of of wave propagation on the surface of opalina wilh depolarization progressing from left to right (

metachronism this relation was used to correclate direction of ciliary beating with the membrane potensial in opolina. The membrane potensial was altered by changes in the KCL concentration of the external medium and the orientation of the metacronal waves was plotted againt membrane potential (figure 10-22) as the membrane is depolarized the direction of the power stroke shifts in a clockwise direction until the beat is directed toward the anterior in the free-swimming cell, this direction of backward locomotion. This shift in the direction of the power stroke is termed ciliary reversal the orientation of the beat is graded whith membrane de polarization in somewhat the same way that muscle contraction is graded with membrane potential. The mechanism that produces reversal of the direction of effective stroke, like the mechanism for muscle contraction requires a certain concentraction of Ca if Ca is absent from the extracelulerfluid the cilia do not reverse their direction of beating in response to depolarization. The higt calcium sensitivity of the ciliary apparatus was demonstrated by Y. Naitoh and H. kaneko (1972) in detergent extracted speciment of paramecium After the membrane is destroyed as a diffusion barrier with triton X-100 ( a nonionic detergent.),the cell can be reactived to swim in a solution of ATP and Mg2+ if the concentration of Ca2= in the reactivation solution is held at lesss than 106 mol/ L the ciliated cells swim forward if it si higher the cilia beat in reverse causing the ciliated cells to swim backward (figure 10-23) because the ciliary apparatus of the extracted paramecium is exposed directly to the reactivation medium (ATP-MgCl2 +CaCl2) these result indicate that the direction of the ciliary power stroke is normally controlled by the internal concentraction of Ca2+ , ATP is required for the calcium actived reversal. If Mg2+ is omittedfrom the reactivation medium the cilia fail to beat but they will shift toward the anterior pointig orientationas the concentration of Ca2+ is increased provinde that ATP is present . In the living ciliate, the concentraktion of free Ca2+ in the cytoplasma is a determined by a balance between efflux of Ca2+ produced by a metabolly