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Functional contributions of HCN channels in the primary auditory neurons of the mouse inner ear.

Kim YH, Holt JR - J. Gen. Physiol. (2013)

Bottom Line: We found that HCN1 is the most prominent subunit contributing to Ih in SGNs.Deletion of Hcn1 resulted in reduced conductance (Gh), slower activation kinetics (τfast), and hyperpolarized half-activation (V1/2) potentials.Together, our data indicate that Ih contributes to SGN membrane properties and plays a role in temporal aspects of signal transmission between the cochlea and the brain, which are critical for normal auditory function.

View Article: PubMed Central - HTML - PubMed

Affiliation: Neuroscience Graduate Program, University of Virginia School of Medicine, Charlottesville, VA 22908, USA.

ABSTRACT
The hyperpolarization-activated current, Ih, is carried by members of the Hcn channel family and contributes to resting potential and firing properties in excitable cells of various systems, including the auditory system. Ih has been identified in spiral ganglion neurons (SGNs); however, its molecular correlates and their functional contributions have not been well characterized. To investigate the molecular composition of the channels that carry Ih in SGNs, we examined Hcn mRNA harvested from spiral ganglia of neonatal and adult mice using quantitative RT-PCR. The data indicate expression of Hcn1, Hcn2, and Hcn4 subunits in SGNs, with Hcn1 being the most highly expressed at both stages. To investigate the functional contributions of HCN subunits, we used the whole-cell, tight-seal technique to record from wild-type SGNs and those deficient in Hcn1, Hcn2, or both. We found that HCN1 is the most prominent subunit contributing to Ih in SGNs. Deletion of Hcn1 resulted in reduced conductance (Gh), slower activation kinetics (τfast), and hyperpolarized half-activation (V1/2) potentials. We demonstrate that Ih contributes to SGN function with depolarized resting potentials, depolarized sag and rebound potentials, accelerated rebound spikes after hyperpolarization, and minimized jitter in spike latency for small depolarizing stimuli. Auditory brainstem responses of Hcn1-deficient mice showed longer latencies, suggesting that HCN1-mediated Ih is critical for synchronized spike timing in SGNs. Together, our data indicate that Ih contributes to SGN membrane properties and plays a role in temporal aspects of signal transmission between the cochlea and the brain, which are critical for normal auditory function.

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HCN1 contributes to membrane properties in adult SGNs. (A) Mean resting potentials recorded from 14 adult SGNs of the indicated genotypes. Number of cells for each genotype is indicated below. *, P < 0.05. (B) Representative membrane responses to hyperpolarizing currents steps recorded from adult WT and Hcn1−/− SGNs. The inset shows the rebound spike on an expanded time scale. (C) Sag potential was significantly (**, P < 0.01) diminished in adult Hcn1−/− SGNs. (D) Mean rebound spike latency for adult Hcn1−/− SGNs showed a significant delay relative to WT SGNs (*, P < 0.05). Error bars equal +1 SD.
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fig11: HCN1 contributes to membrane properties in adult SGNs. (A) Mean resting potentials recorded from 14 adult SGNs of the indicated genotypes. Number of cells for each genotype is indicated below. *, P < 0.05. (B) Representative membrane responses to hyperpolarizing currents steps recorded from adult WT and Hcn1−/− SGNs. The inset shows the rebound spike on an expanded time scale. (C) Sag potential was significantly (**, P < 0.01) diminished in adult Hcn1−/− SGNs. (D) Mean rebound spike latency for adult Hcn1−/− SGNs showed a significant delay relative to WT SGNs (*, P < 0.05). Error bars equal +1 SD.

Mentions: To investigate whether the Ih effects on resting potential, sag potential, and spike latency were caused by HCN1 or HCN2, we examined adult SGNs of WT, Hcn1−/−, and Hcn2−/− mice. SGNs from adult Hcn1−/− mice had resting potentials that were significantly more hyperpolarized than both WT and Hcn2−/− SGNs (Fig. 11 A). Hyperpolarizing current steps evoked a prominent sag (Fig. 11 B) that decayed more quickly than the sag recorded from neonatal SGNs (Fig. 8 B), consistent with the faster Ih activation kinetics in adult SGNs (Fig. 7 E). The amplitude of the sag potential was also significantly reduced in adult Hcn1−/− SGNs relative to WT and Hcn2−/− SGNs (Fig. 11 C). Lastly, we noted a delay in rebound spike latency in adult Hcn1−/− SGNs (Fig. 11, B and D), which confirms a prominent role for HCN1 in spike timing in adult SGNs.


Functional contributions of HCN channels in the primary auditory neurons of the mouse inner ear.

Kim YH, Holt JR - J. Gen. Physiol. (2013)

HCN1 contributes to membrane properties in adult SGNs. (A) Mean resting potentials recorded from 14 adult SGNs of the indicated genotypes. Number of cells for each genotype is indicated below. *, P < 0.05. (B) Representative membrane responses to hyperpolarizing currents steps recorded from adult WT and Hcn1−/− SGNs. The inset shows the rebound spike on an expanded time scale. (C) Sag potential was significantly (**, P < 0.01) diminished in adult Hcn1−/− SGNs. (D) Mean rebound spike latency for adult Hcn1−/− SGNs showed a significant delay relative to WT SGNs (*, P < 0.05). Error bars equal +1 SD.
© Copyright Policy - openaccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC3753603&req=5

fig11: HCN1 contributes to membrane properties in adult SGNs. (A) Mean resting potentials recorded from 14 adult SGNs of the indicated genotypes. Number of cells for each genotype is indicated below. *, P < 0.05. (B) Representative membrane responses to hyperpolarizing currents steps recorded from adult WT and Hcn1−/− SGNs. The inset shows the rebound spike on an expanded time scale. (C) Sag potential was significantly (**, P < 0.01) diminished in adult Hcn1−/− SGNs. (D) Mean rebound spike latency for adult Hcn1−/− SGNs showed a significant delay relative to WT SGNs (*, P < 0.05). Error bars equal +1 SD.
Mentions: To investigate whether the Ih effects on resting potential, sag potential, and spike latency were caused by HCN1 or HCN2, we examined adult SGNs of WT, Hcn1−/−, and Hcn2−/− mice. SGNs from adult Hcn1−/− mice had resting potentials that were significantly more hyperpolarized than both WT and Hcn2−/− SGNs (Fig. 11 A). Hyperpolarizing current steps evoked a prominent sag (Fig. 11 B) that decayed more quickly than the sag recorded from neonatal SGNs (Fig. 8 B), consistent with the faster Ih activation kinetics in adult SGNs (Fig. 7 E). The amplitude of the sag potential was also significantly reduced in adult Hcn1−/− SGNs relative to WT and Hcn2−/− SGNs (Fig. 11 C). Lastly, we noted a delay in rebound spike latency in adult Hcn1−/− SGNs (Fig. 11, B and D), which confirms a prominent role for HCN1 in spike timing in adult SGNs.

Bottom Line: We found that HCN1 is the most prominent subunit contributing to Ih in SGNs.Deletion of Hcn1 resulted in reduced conductance (Gh), slower activation kinetics (τfast), and hyperpolarized half-activation (V1/2) potentials.Together, our data indicate that Ih contributes to SGN membrane properties and plays a role in temporal aspects of signal transmission between the cochlea and the brain, which are critical for normal auditory function.

View Article: PubMed Central - HTML - PubMed

Affiliation: Neuroscience Graduate Program, University of Virginia School of Medicine, Charlottesville, VA 22908, USA.

ABSTRACT
The hyperpolarization-activated current, Ih, is carried by members of the Hcn channel family and contributes to resting potential and firing properties in excitable cells of various systems, including the auditory system. Ih has been identified in spiral ganglion neurons (SGNs); however, its molecular correlates and their functional contributions have not been well characterized. To investigate the molecular composition of the channels that carry Ih in SGNs, we examined Hcn mRNA harvested from spiral ganglia of neonatal and adult mice using quantitative RT-PCR. The data indicate expression of Hcn1, Hcn2, and Hcn4 subunits in SGNs, with Hcn1 being the most highly expressed at both stages. To investigate the functional contributions of HCN subunits, we used the whole-cell, tight-seal technique to record from wild-type SGNs and those deficient in Hcn1, Hcn2, or both. We found that HCN1 is the most prominent subunit contributing to Ih in SGNs. Deletion of Hcn1 resulted in reduced conductance (Gh), slower activation kinetics (τfast), and hyperpolarized half-activation (V1/2) potentials. We demonstrate that Ih contributes to SGN function with depolarized resting potentials, depolarized sag and rebound potentials, accelerated rebound spikes after hyperpolarization, and minimized jitter in spike latency for small depolarizing stimuli. Auditory brainstem responses of Hcn1-deficient mice showed longer latencies, suggesting that HCN1-mediated Ih is critical for synchronized spike timing in SGNs. Together, our data indicate that Ih contributes to SGN membrane properties and plays a role in temporal aspects of signal transmission between the cochlea and the brain, which are critical for normal auditory function.

Show MeSH
Related in: MedlinePlus