title: Mechanism of spontaneous activity in afferent neurons of the zebrafish lateral-line organ.
abstract: Many auditory, vestibular, and lateral-line afferent neurons display spontaneous action potentials. This spontaneous spiking is thought to result from hair-cell glutamate release in the absence of stimuli. Spontaneous release at hair-cell resting potentials presumably results from Ca(V)1.3 L-type calcium channel activity. Here, using intact zebrafish larvae, we recorded robust spontaneous spiking from lateral-line afferent neurons in the absence of external stimuli. Consistent with the above assumptions, spiking was absent in mutants that lacked either Vesicular glutamate transporter 3 (Vglut3) or Ca(V)1.3. We then tested the hypothesis that spontaneous spiking resulted from sustained Ca(V)1.3 activity due to depolarizing currents that are active at rest. Mechanotransduction currents (I(MET)) provide a depolarizing influence to the resting potential. However, following block of I(MET), spontaneous spiking persisted and was characterized by longer interspike intervals and increased periods of inactivity. These results suggest that an additional depolarizing influence maintains the resting potential within the activation range of Ca(V)1.3. To test whether the hyperpolarization-activated cation current, I(h) participates in setting the resting potential, we applied I(h) antagonists. Both ZD7288 and DK-AH 269 reduced spontaneous activity. Finally, concomitant block of I(MET) and I(h) essentially abolished spontaneous activity, ostensibly by hyperpolarization outside of the activation range for Ca(V)1.3. Together, our data support a mechanism for spontaneous spiking that results from Ca(2+)-dependent neurotransmitter release at hair-cell resting potentials that are maintained within the activation range of Ca(V)1.3 channels through active I(MET) and I(h).
authors.affiliation: Howard Hughes Medical Institute, Oregon Health and Science University, Portland, Oregon 97239, USA. trapanij@ohsu.edu
authors.forename: Josef G
authors.initials: JG
authors.lastname: Trapani
authors.forename: Teresa
authors.initials: T
authors.lastname: Nicolson
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000502:physiology*; D054815:Cyclic Nucleotide-Gated Cation Channels / Q000502:physiology*; D004558:Electric Stimulation / Q000379:methods; D004594:Electrophysiology; D006198:Hair Cells, Auditory / Q000502:physiology; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D053403:Lateral Line System / Q000187:drug effects / Q000502:physiology*; D040542:Mechanotransduction, Cellular / Q000187:drug effects / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology*; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology*; D010812:Physical Stimulation / Q000379:methods; D015221:Potassium Channels / Q000502:physiology*; D011743:Pyrimidines / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050496:Vesicular Glutamate Transport Proteins / Q000172:deficiency / Q000235:genetics; D015027:Zebrafish
chemical_list: D001552:Benzazepines; D020746:Calcium Channels, L-Type; D054815:Cyclic Nucleotide-Gated Cation Channels; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D015221:Potassium Channels; D011743:Pyrimidines; D050496:Vesicular Glutamate Transport Proteins; C082246:ICI D2788; C087873:DK-AH 268