Pharmacology and Neurotransmission of Sensory Transduction in the Inner Ear

Bledsoe, Sanford C.

doi:10.1055/s-0028-1091448

Cited by 4 publications

(2 citation statements)

References 78 publications

(120 reference statements)

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“…Electron microscopic studies indicate that individual hair cells in various species contain from 1 to nearly 100 presynaptic active zones (Miller and Beck, 1988), each associated with a swarm of synaptic vesicles and at least 1 synaptic body, a spherical, osmiophilic structure of unknown function that resembles the presynaptic specializations of photoreceptors and certain neurons. Synaptic transmission occurs by quanta1 release (Ishii et al,197 1) ofan unknown neurotransmitter, probably an amino acid (Cochran et al, 1987; but see Sewell and Mroz, 1987; for reviews, see Bledsoe, 1986;Roberts et al, 1988). As at other chemical synapses, the entry of Ca2+ through voltagegated channels presumably initiates the release of transmitter.…”

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Colocalization of ion channels involved in frequency selectivity and synaptic transmission at presynaptic active zones of hair cells

1990

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Calcium ions serve as intracellular messengers in 2 activities of hair cells: in conjunction with Ca2(+)-activated K+ channels, they produce the electrical resonance that tunes each cell to a specific frequency of stimulation, and they trigger the release of a chemical synaptic transmitter. Our experiments indicate that both of these functions are conducted within a region that extends a few hundred nanometers around each presynaptic active zone. In focal electrical recordings from the plasma membranes of isolated anuran hair cells, we found nearly all of a cell's Ca2+ channels and Ca2(+)-activated K+ channels clumped at a fixed ratio in an average of 20 clusters on the basolateral membrane surface. Because serial-section electron microscopy indicated that each hair cell has approximately 19 afferent synaptic contacts with a similar distribution upon its basolateral surface, we conclude that the channel clusters coincide with synaptic active zones. Ensemble-variance analysis of current fluctuations indicated that each cell has a total of approximately 1800 Ca2+ channels and approximately 700 Ca2(+)-activated K+ channels; if these are uniformly divided, we estimate that each channel cluster contains approximately 90 Ca2+ and approximately 40 Ca2(+)-activated K+ channels. Freeze-fracture electron microscopy demonstrated an average of 133 large intramembrane particles in the presynaptic membrane at each active zone, an observation that suggests that the particles are the clustered channels. We used the K+ channel's sensitivity to intracellular Ca2+ to assay the concentration of free Ca2+ in the presynaptic cytoplasm, which we found to vary between 10 microM and 1 mM over the physiological range of membrane potentials. The inferred concentrations agreed with the values predicted for free diffusion of Ca2+ away from Ca2+ channels scattered randomly within a 300-nm-diameter synaptic active zone. The close association among Ca2+ channels, Ca2(+)-activated K+ channels, and synaptic active zones is necessary both for the rapid activation of K+ currents required in electrical resonance and for the transmission at afferent synapses of information about the phases of high-frequency stimuli.

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Colocalization of ion channels involved in frequency selectivity and synaptic transmission at presynaptic active zones of hair cells

1990

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“…The identity of the primary afferent transmitter released by hair cells in octavolateralis organs, including the amphibian lateral line, is not known, though evidence suggests that it is an excitatory amino acid, possibly L-glutamate (Bobbin et al, 1985b;Bledsoe, 1986;Bledsoe et al, 1988). Recently, Guth and associates (Norris et al, 1987) suggested that histamine may play a role as a hair-cell transmitter in the semicircular canal of the frog.…”

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Analysis of histamine as a hair-cell transmitter in the lateral line of Xenopus laevis

1989

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The actions of histamine and histamine antagonists on afferent nerve activity were investigated in the lateral line of Xenopus laevis. Histamine (0.002-2.0 mM) had no effect on spontaneous activity or excitatory responses to water motion. In contrast, pyrilamine, an H1 receptor antagonist, suppressed spontaneous activity beginning at 0.01-0.05 mM. Below 0.3 mM the suppression was often preceded by a small excitatory response and responses to high (24-30 dB re threshold), but not low (0-18 dB) levels of water motion were selectively suppressed. Higher concentrations (0.3-2.0 mM) abolished spontaneous activity and suppressed responses at all levels of water motion. Cimetidine, an H2 receptor antagonist, had similar actions but was one-tenth as potent as pyrilamine. Tetrodotoxin (0.001-0.1 microM), which blocks voltage-sensitive Na+ channels, mimicked the suppressive effects of the histamine antagonists. Histamine (2.0 mM) failed to block the actions of pyrilamine (0.1 mM) indicating its effects are mediated through a mechanism other than histamine receptors. In addition, pyrilamine (0.05-0.1 mM) non-selectively suppressed excitation to exogenously applied L-glutamate (1.0-2.0 mM), L-aspartate (1.0-2.0 mM), kainate (0.005-0.01 mM), and quisqualate (0.002-0.005 mM) and altered responses to N-methyl-D-aspartate (0.5-1.0 mM). The results are inconsistent with histamine being a transmitter in the Xenopus lateral line and reveal that the actions of histamine antagonists are nonspecific, possibly due, in part, to blockade of voltage-sensitive Na+ channels.

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