Mechanism of spontaneous activity in afferent neurons of the zebrafish lateral-line organ.
Mechanism of spontaneous activity in afferent neurons of the zebrafish lateral-line organ.
复制标题
DOI:
10.1523/jneurosci.3369-10.2011
复制
发表时间:
2011-02-02
期刊:
影响因子:
--
通讯作者:
Nicolson T
中科院分区:
文献类型:
--
作者:
Trapani JG;Nicolson T
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 CaV1.3 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 CaV1.3. We then tested the hypothesis that spontaneous spiking resulted from sustained CaV1.3 activity due to depolarizing currents that are active at rest. Mechanotransduction currents (IMET) provide a depolarizing influence to the resting potential. However, following block of IMET, spontaneous spiking persisted and was characterized by longer inter-spike intervals and increased periods of inactivity. These results suggest that an additional depolarizing influence maintains the resting potential within the activation range of CaV1.3. To test whether the hyperpolarization-activated cation current, Ih participates in setting the resting potential, we applied Ih antagonists. Both ZD7288 and DK-AH 269 reduced spontaneous activity. Finally, concomitant block of IMET and Ih essentially abolished spontaneous activity, ostensibly by hyperpolarization outside of the activation range for CaV1.3. Together, our data support a mechanism for spontaneous spiking that results from Ca2+-dependent neurotransmitter release at hair-cell resting potentials that are maintained within the activation range of CaV1.3 channels through active IMET and Ih.