Genomic structure, cochlear expression, and mutation screening of <i>KCNK6</i>, a candidate gene for DFNA4

Mhatre, Anand N.; Jiang, Li; Chen, Arthur F.; Yost, C. Spencer; Smith, Richard J.H.; Kindler, Christoph; Lalwani, Anil K.

doi:10.1002/jnr.10839

Cited by 11 publications

(9 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Consequently, they did not investigate K 2P 6.1i in the vestibular periphery. Mhatre et al, 2004 showed that Kcnk6 mRNA is expressed in the mouse cochlea and that K 2P 6.1i is predominantly in the stria vascularis. We detected K 2P 6.1i in the vestibular transitional cells and in nerve terminals in the vestibular epithelia.…”

Section: Discussionmentioning

confidence: 99%

Distribution of two-pore-domain potassium channels in the adult rat vestibular periphery

et al. 2008

View full text Add to dashboard Cite

Constitutively active background or "leak" two-pore-domain potassium (K + ) channels (Kcnk family), as defined by lack of voltage and time dependency are central to electrical excitability of cells by controlling resting membrane potential and membrane resistance. Inhibition of these channels by several neurotransmitters, e.g. glutamate, or acetylcholine, induces membrane depolarization and subsequent action potential firing as well as increases membrane resistance amplifying responses to synaptic inputs. In contrast, their opening contributes to hyperpolarization. Because of their central role in determining cellular excitability and response to synaptic stimulation, these channels likely play a role in the differential effects of vestibular efferent neurons on afferent discharge. Microarray data from previous experiments showed Kcnk 1,2,3,6,12 and 15 mRNA in Scarpa's ganglia. Real-time RT-PCR showed Kcnk 1,2,3,6,12 and 15 mRNA expression in Scarpa's ganglia and Kcnk 1,2,3,6,12 but not 15 mRNA expression in the crista ampullaris. We studied the distribution of two-pore-domain potassium channels K 2P

show abstract

Section: Discussionmentioning

confidence: 99%

Distribution of two-pore-domain potassium channels in the adult rat vestibular periphery

et al. 2008

View full text Add to dashboard Cite

show abstract

“…2000; Vale and Sanes 2002), in ion channels (Storey et al . 2002; Mhatre et al . 2004), in transcription factors (Illing et al .…”

mentioning

confidence: 99%

“…Deafness (full or partial) and noise over-stimulation have been shown to lead to plastic changes in the mature central auditory pathways (Syka 2002;Moller 2005). Changes that have been reported following deafness include changes in the tonotopic map (Robertson et al 1989;Rajan et al 1993), in cell size (Sie and Rubel 1992;Dodson et al 1994;Lustig et al 1994;Lesperance et al 1995;Willott and Bross 1996;Moore et al 1997;Niparko and Finger 1997;Araki et al 1998;Edmonds et al 1999;Niparko 1999;Nishiyama et al 2000), changes in synaptic contacts and synapse morphology (Kazee et al 1995;Huchton et al 1997;Ryugo et al 1997;Niparko 1999;Russell and Moore 2002;Lee et al 2003), in neurotransmitters and receptors as well as their release, uptake and binding (Caspary et al 1995;Milbrandt et al 2000;Potashner et al 2000;Vale and Sanes 2002), in ion channels (Storey et al 2002;Mhatre et al 2004), in transcription factors (Illing et al 1999;Illing and Michler 2001;von Hehn et al 2004), in oxygen reactive species (Ohlemiller and Dugan 1999;Shi et al 2002), and in stress response molecules (Myers et al 1992;Billings et al 1995;Verstreken et al 1996;Oh et al 2000;Van Campen et al 2002;…”

mentioning

confidence: 99%

Deafness‐related plasticity in the inferior colliculus: gene expression profiling following removal of peripheral activity

Holt

Asako

Lomax

et al. 2005

Journal of Neurochemistry

View full text Add to dashboard Cite

The inferior colliculus (IC) is a major center of integration in the ascending as well as descending auditory pathways, where both excitatory and inhibitory amino acid neurotransmitters play a key role. When normal input to the auditory system is decreased, the balance between excitation and inhibition in the IC is disturbed. We examined global changes in gene expression in the rat IC 3 and 21 days following bilateral deafening, using Affymetrix GeneChip arrays and focused our analysis on changes in expression of neurotransmission-related genes. Over 1400 probe sets in the Affymetrix Rat Genome U34A Array were identified as genes that were differentially expressed. These genes encoded proteins previously reported to change as a consequence of deafness, such as calbindin, as well as proteins not previously reported to be modulated by deafness, such as clathrin. A subset of 19 differentially expressed genes was further examined using quantitative RT-PCR at 3, 21 and 90 days following deafness. These included several GABA, glycine, glutamate receptor and neuropeptide-related genes.Expression of genes for GABA-A receptor subunits b2, b3, and c2, plus ionotropic glutamate receptor subunits AMPA 2, AMPA 3, and kainate 2, increased at all three times. Expression of glycine receptor a1 initially declined and then later increased, while a2 increased sharply at 21 days. Glycine receptor a3 increased between 3 and 21 days, but decreased at 90 days. Of the neuropeptide-related genes tested with qRT-PCR, tyrosine hydroxylase decreased approximately 50% at all times tested. Serotonin receptor 2C increased at 3, 21, and 90 days. The 5B serotonin receptor decreased at 3 and 21 days and returned to normal by 90 days. Of the genes tested with qRT-PCR, only glycine receptor a2 and serotonin receptor 5B returned to normal levels of expression at 90 days. Changes in GABA receptor b3, GABA receptor c2, glutamate receptor 2/3, enkephalin, and tyrosine hydroxylase were further confirmed using immunocytochemistry.

show abstract

“…TASK-1, TREK-1, TWIK-1, and TWIK-2 expression have been found by RT-PCR and immunolocalization methods in various cochlear structures including sensory and supporting cells of the organ of Corti, spiral ganglion, stria vascularis, Reissner's membrane, inner and outer sulcus cell, and cochlear nucleus. 47,[93][94][95][96] Although no association has yet been made between these genes and heritable hearing loss syndromes, 95 acute toxicity produced by high local anesthetic concentrations may occur through disinhibition of these K 2P channels.…”

Section: K 2p Channels and Local Anesthetic Toxicitymentioning

confidence: 99%

Two-Pore Domain Potassium Channels: New Sites of Local Anesthetic Action and Toxicity

Kindler

Yost

2005

Regional Anesthesia and Pain Medicine

View full text Add to dashboard Cite

Potassium (K+) channels form the largest family of ion channels with more than 70 such genes identified in the human genome. They are organized in 3 superfamilies according to their predicted membrane topology: (1) subunits with 6 membrane-spanning segments and 1-pore domain, (2) subunits with 2 membrane-spanning segments and 1-pore domain, and (3) subunits with 4 membrane-spanning segments and 2-pore domains arrayed in a tandem position. The last family has most recently been identified and comprises the so-called 2-pore domain potassium (K2P) channels, believed responsible for background or leak K+ currents. Despite their recent discovery, interest in them is growing rapidly with more than 270 references in the literature reported (www.ipmc.cnrs.fr/~duprat/2p/ref2p.htm#2P, accessed October 30, 2004). K2P channels are widely expressed in the central nervous system and are involved in the control of the resting membrane potential and the firing pattern of excitable cells. This article will therefore review recent findings on actions of local anesthetics with respect to 2P channels. It begins with an overview of the role of background K+ channels in neuronal excitability and nerve conduction and is followed by a description of the K2P channel family including experimental evidence for the contribution of K2P channels to the mechanism of action and toxicity of local anesthetics.

show abstract

Genomic structure, cochlear expression, and mutation screening of KCNK6, a candidate gene for DFNA4

Cited by 11 publications

References 16 publications

Distribution of two-pore-domain potassium channels in the adult rat vestibular periphery

Distribution of two-pore-domain potassium channels in the adult rat vestibular periphery

Deafness‐related plasticity in the inferior colliculus: gene expression profiling following removal of peripheral activity

Two-Pore Domain Potassium Channels: New Sites of Local Anesthetic Action and Toxicity

Contact Info

Product

Resources

About