Deafness associated changes in expression of two-pore domain potassium channels in the rat cochlear nucleus

Abstract

Two-pore domain potassium channels ( ) play an important role in setting resting membrane potential by regulating background leakage of potassium ions, which in turn controls neuronal excitability. To determine whether these channels contribute to activity-dependent plasticity following deafness, we used quantitative real-time PCR to examine the expression of 10 subunits in the rat cochlear nucleus at 3 days, 3 weeks and 3 months after bilateral cochlear ablation. There was a large sustained decrease in the expression of TASK-5, a subunit that is predominantly expressed in auditory brain stem neurons, and in the TASK-1 subunit which is highly expressed in several types of cochlear nucleus neurons. TWIK-1 and THIK-2 also showed significant decreases in expression that were maintained across all time points. TWIK-2, TREK-1 and TREK-2 showed no significant change in expression at 3 days but showed large decreases at 3 weeks and 3 months following deafness. TRAAK and TASK-3 subunits showed significant decreases at 3 days and 3 weeks following deafness, but these differences were no longer significant at 3 months. Dramatic changes in expression of subunits suggest these channels may play a role in deafness-associated changes in the excitability of cochlear nucleus neurons.

Deafness associated changes in two-pore domain potassium channels in the rat inferior colliculus

“…Previous RT-PCR and in situ hybridization studies have revealed that TWIK-1 is present in the mammalian brain and also in a wide variety of tissues outside the nervous system (Lesage et al, 1996;Orias et al, 1997, Arrighi et al, 1998 Wang et al,1998;Medhurst et al, 2001 andTalley et al, 2001). TWIK-1 expression has been previously shown in the cochlear nucleus using PCR (Holt et al, 2006) and in the inner ear and cochlear nucleus using in situ hybridization (Nicolas MT et al, 2003;Talley et al, 2001). In the present study, a decrease in TWIK-1 expression was found which did not reach significance until 3 weeks following deafening (24% decrease, p=0.003) and remained significantly decreased by 20% (p=0.002) at 3 months following deafness (Figure 2A).…”

“…These subunits were also shown to be expressed in the rat cochlear nucleus with PCR (Holt et al, 2006) and TREK-1 immunostaining was shown in the rat cochlea (Kanjhan et al, 2004a) and cochlear nucleus (Kanjhan et al, 2004b). In the current study all three subunits are expressed in the IC ( Figure 2B).…”

“…The expression of K 2p channels can be regulated by biochemical and physical cues as well as activity (Enyeart et al, 2003;Holt et al, 2006;Kang et al, 2004;Li et al, 2005;Liu and Saint, 2004;Xu et al, 2004 andYeom et al, 2005). These channels could play a role in activitydependent synaptic plasticity, where intracellular signaling induced by changes in activity level can alter the properties of target neurons.…”

“…Tissue from three animals (six IC) was combined into a pool and homogenized in Trizol (Invitrogen) for 10 sec. RNA was isolated as described previously (Holt et al, 2006). Inclusion of an RNA pool in the study depended on the integrity of the 18S and 28S ribosomal RNA bands, determined using a RNA 6000 Nano LabChip in a Bioanalyzer (Agilent, Palo Alto, CA).…”

“…Gene expression for TWIK-1, TREK-1 (K 2p 2.1, KNCK2), TASK-1, TRAAK (K 2p 4.1, KCNK4), TWIK-2 (K 2p 6.1, KCNK6), TASK-3, TREK-2 (K 2p 10.1, kcnk10), THIK-2 (K 2p 12.1, KCNK12), THIK-1 (K 2p 13.1, KCNK13) and TASK-5 mRNAs has recently been reported for the rat cochlear nucleus (Holt et al, 2006) and TASK-1 was reported as selectively elevated in spherical bushy cells (Pal et al, 2005).…”