Pharmacology of Acetylcholine-Mediated Cell Signaling in the Lateral Line Organ Following Efferent Stimulation

Abstract

of acetylcholine-mediated cell signaling in the lateral line organ following efferent stimulation. J Neurophysiol 93: [2541][2542][2543][2544][2545][2546][2547][2548][2549][2550][2551] 2005. First published December 22, 2004; doi:10.1152/jn.01283. 2004. Cholinergic efferent fibers modify hair cell responses to mechanical stimulation. It is hypothesized that calcium entering the hair cell through a nicotinic receptor activates a small-conductance (SK), calcium-activated potassium channel to hyperpolarize the hair cell. The calcium signal may be amplified by calcium-induced calcium release from the synaptic cisternae. Pharmacological tests of these ideas in the intact cochlea have been technically difficult because of the complex and fragile structure of the mammalian inner ear. We turned to the Xenopus laevis lateral line organ, whose simplicity and accessibility make it a model for understanding hair cell organ function in a relatively intact system. Drugs were applied to the inner surface of the skin while monitoring the effects of efferent stimulation on afferent fiber discharge rate. Efferent effects were blocked by antagonists of SK channels including apamin (EC 50 ϭ 0.5 M) and dequalinium (EC 50 ϭ 12 M). The effect of apamin was not enhanced by co-administration of phenylmethylsulfonyl fluoride, a proteolysis inhibitor. Efferent effects were attenuated by ryanodine, an agent that can interfere with calcium-induced calcium release, although relatively high (mM) concentrations of ryanodine were required. Fluorescent cationic styryl dyes, 4-di-2-asp and fm 1-43, blocked efferent effects, although it was not possible to observe specific entry of the dye into the base of hair cells. These pharmacological findings in the Xenopus lateral line organ support the hypothesis that effects of efferent stimulation are mediated by calcium entry through the nicotinic receptor via activation of SK channels and suggest the generality of this mechanism in meditating cholinergic efferent effects.

Mechanisms of Efferent-Mediated Responses in the Turtle Posterior Crista

“…A similar phenomenon is seen in frog vestibular-nerve fibers (Sugai et al, 1991) and lateral-line afferents (Dawkins et al, 2005). In our preparation, the excitation arises presynaptically and depends on the preceding inhibition.…”

“…In auditory (Furukawa, 1981;Art et al, 1985;Fuchs and Murrow, 1992;Oliver et al, 2000), vibratory (Sugai et al, 1991) and lateral-line (Russell, 1968;Dawkins et al, 2005) receptors, efferents inhibit afferent discharge. Efferentmediated responses in vestibular organs are more diverse, consisting of excitation (mammals, Goldberg and Fernandez, 1980;toadfish, Boyle and Highstein, 1990) or excitation and inhibition in different afferents (frog, Rossi et al, 1980;turtle, Brichta and Goldberg, 2000b;pigeon, Dickman and Correia, 1993).…”

A Novel α-Conotoxin, PeIA, Cloned from Conus pergrandis, Discriminates between Rat α9α10 and α7 Nicotinic Cholinergic Receptors

“…Higher vertebrate ␣9 and ␣9␣10 nAChRs mediate efferent cholinergic inhibition at cochlear and vestibular hair cells (3,7,28,29,41). The cholinergic pharmacology of efferent block in the fish lateral line organ is similar to that in hair cells of the cochlea, indicating that the same nicotinic cholinergic receptor is likely involved (54,55). The proper orientation of mechanosensory hair cells along the lateral line organ of a fish is essential for the ability of the animal to sense directional water movements.…”

SK2 channels are required for function and long-term survival of efferent synapses on mammalian outer hair cells

“…The role, if any, of the early depolarizing response generated by the initial calcium entry through the ACh-activated channel is unknown. However, this synaptic property is shared by the inner ears of mammals, birds, fish, amphibia, and reptiles (Fuchs and Murrow, 1992a, b; Art et al, 1995; Blanchet et al, 1996; Dulon and Lenoir, 1996; Nenov et al, 1996; Dulon et al, 1998; Kros et al, 1998; Oliver et al, 2000; Dawkins et al, 2005; Holt et al, 2006), and therefore represents a basic mechanism of action underlying efferent feedback on hearing organs and perhaps even a conserved interdependent macromolecular structure important for hair cell cholinergic synapse assembly. In order to better understand the functional significance to hearing of generating a postsynaptic response of this type, as well as to investigate the consequences of the early calcium entry through the ACh-activated channels, we used mice carrying a null mutation for KCNN2, the gene for SK2.…”