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Ether-à-go-go-related gene K+ channels contribute to threshold excitability of mouse auditory brainstem neurons

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journal contribution
posted on 02.06.2010, 14:54 by Rachael M. Hardman, Ian D. Forsythe
The ionic basis of excitability requires identification and characterisation of expressed channels and their specific roles in native neurons. We have exploited principal neurons of the medial nucleus of the trapezoid body (MNTB) as a model system for examining voltage-gated K+ channels, because of their known function and simple morphology. Here we show that the ether-à-go-go-related gene family (kcnh, ERG, Kv11) compliment Kv1 channels in regulating neuronal excitability around threshold voltages. Using whole-cell patch clamp from brainstem slices, the selective ERG antagonist E-4031 reduced action potential (AP) threshold and increased firing on depolarisation. In P12 mice, under voltage-clamp with elevated [K+]o (20 mM), a slowly deactivating current was blocked by E-4031- or terfenadine; (V0.5,act = -58.4 ± 0.9 mV, V0.5,inact = -76.1 ± 3.6 mV). Deactivation followed a double exponential time course (τslow = 113.8 ± 6.9 ms, τfast = 33.2 ± 3.8 ms at -110 mV, τfast 46% peak amplitude). In P25 mice, deactivation was best fit by a single exponential (τfast = 46.8 ± 5.8 ms at -110 mV). Quantitative rt-PCR showed that ERG1 and ERG3 were the predominant mRNAs and immunohistochemistry showed expression as somatic plasma membrane puncta on principal neurons. We conclude that ERG currents complement Kv1 currents in limiting AP firing at around threshold; ERG may have a particular role during periods of high activity when [K+]o is elevated. These ERG currents suggest a potential link between auditory hyperexcitability and acoustic startle triggering of cardiac events in familial LQT2.

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Citation

The Journal of Physiology, 2009, 587 (11), pp. 2487-2497.

Published in

The Journal of Physiology

Publisher

Blackwell Publishing

issn

0022-3751

Copyright date

2009

Available date

02/06/2010

Publisher version

http://onlinelibrary.wiley.com/doi/10.1113/jphysiol.2009.170548/abstract

Language

en

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