Slack and Slick K<sub>Na</sub>channels are required for the depolarizing afterpotential of acutely isolated, medium diameter rat dorsal root ganglion neurons<sup>1</sup>

Gao, Shangbang; Wu, Ying; Lü, Caixia; Guo, Zhenhui; Li, Chenhong; Ding, Jiuping

doi:10.1111/j.1745-7254.2008.00842.x

Cited by 30 publications

(32 citation statements)

References 21 publications

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“…• K Na Channels Are Modulated by NAD ϩ nohistochemical data and is similar to what has been reported earlier (Bischoff et al, 1998;Gao et al, 2008). The K Na channel EC 50 s for Na ϩ was determined to be 53 mM (n ϭ 6) and 55 mM (n ϭ 6) in small neurons (Fig.…”

Section: K Na Channels In Drg Neuronssupporting

confidence: 72%

“…Previous work has documented that K Na channels can be recorded in small-and medium-sized DRG neurons (Bischoff et al, 1998;Gao et al, 2008), and we have now demonstrated that K Na channels are also present in large, proprioceptive DRG neurons. The Na ϩ -doseresponse relationship for K Na channels for both small and large DRG neurons was determined to be similar.…”

Section: Discussionmentioning

confidence: 62%

“…Among DRG neurons, K Na channels have only been studied in rat neonatal small DRG neurons (Bischoff et al, 1998) or in adult medium-sized DRG neurons (Gao et al, 2008). In this study, we show that Slack K Na channels are ubiquitously expressed in adult rat DRG neurons.…”

Section: Introductionmentioning

confidence: 73%

“…Precedence for modulation by NAD ϩ , NADP ϩ , or NADH has been set with a variety of K ϩ channels, including the K ϩ transport-nucleotide-binding channel, the ATP-sensitive K ϩ channel, and the Ca 2ϩ -activated K ϩ channel (Lee et al, 1994;Roosild et al, 2002;Dabrowski et al, 2003;Tipparaju et al, 2005). If K Na channels control DRG neuronal resting membrane potential (Bischoff et al, 1998) and/or limit the DAP (Gao et al, 2008), then reduced K Na activity as a result of decreased NAD ϩ modulation will lead to DRG neuronal hyperexcitability and spontaneous firing. As we have now shown, K Na channels are abundantly and ubiquitously expressed in DRG neurons.…”

Section: Discussionmentioning

confidence: 99%

“…In some neurons, these channels have been suggested to control the resting membrane potential (Haimann et al, 1992;Koh et al, 1994;Bischoff et al, 1998). Recent evidence indicates that in adult medium-sized dorsal root ganglion (DRG) neurons, a single Na ϩ -dependent action potential can elicit a K Na current, and K Na channels were suggested to regulate the depolarizing after potential (DAP) (Gao et al, 2008). However, it has been difficult to reconcile these diverse physiological functions with one apparent property of K Na channels: their requirement for high concentrations of [Na ϩ ] i to activate.…”

Section: Introductionmentioning

confidence: 99%

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NAD⁺Activates K_NaChannels in Dorsal Root Ganglion Neurons

Picchione²,

2009

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Although sodium-activated potassium channels (K Na ) have been suggested to shape various firing patterns in neurons, including action potential repolarization, their requirement for high concentrations of Na ϩ to gate conflicts with this view. We characterized K Na channels in adult rat dorsal root ganglion (DRG) neurons. Using immunohistochemistry, we found ubiquitous expression of the Slack K Na channel subunit in small-, medium-, and large-diameter DRG neurons. Basal K Na channel activity could be recorded from cell-attached patches of acutely dissociated neurons bathed in physiological saline, and yet in excised inside-out membrane patches, the Na ϩ EC 50 for K Na channels was typically high, ϳ50 mM. In some cases, however, K Na channel activity remained considerable after initial patch excision but decreased rapidly over time. Channel activity was restored in patches with high Na ϩ . The channel rundown after initial excision suggested that modulation of channels might be occurring through a diffusible cytoplasmic factor. Sequence analysis indicated that the Slack channel contains a putative nicotinamide adenine dinucleotide (NAD ϩ )-binding site; accordingly, we examined the modulation of native K Na and Slack channels by NAD ϩ . In inside-out-excised neuronal patch recordings, we found a decrease in the Na ϩ EC 50 for K Na channels from ϳ50 to ϳ20 mM when NAD ϩ was included in the perfusate. NAD ϩ also potentiated recombinant Slack channel activity. NAD ϩ modulation may allow K Na channels to operate under physiologically relevant levels of intracellular Na ϩ and hence provides an explanation as to how K Na channel can control normal neuronal excitability.

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Section: K Na Channels In Drg Neuronssupporting

confidence: 72%

Section: Discussionmentioning

confidence: 62%

Section: Introductionmentioning

confidence: 73%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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NAD⁺Activates K_NaChannels in Dorsal Root Ganglion Neurons

Picchione²,

2009

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Differential distribution of the sodium‐activated potassium channels slick and slack in mouse brain

Rizzi

Knaus

Schwarzer

2015

J of Comparative Neurology

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The sodium‐activated potassium channels Slick (Slo2.1, KCNT2) and Slack (Slo2.2, KCNT1) are high‐conductance potassium channels of the Slo family. In neurons, Slick and Slack channels are involved in the generation of slow afterhyperpolarization, in the regulation of firing patterns, and in setting and stabilizing the resting membrane potential. The distribution and subcellular localization of Slick and Slack channels in the mouse brain have not yet been established in detail. The present study addresses this issue through in situ hybridization and immunohistochemistry. Both channels were widely distributed and exhibited distinct distribution patterns. However, in some brain regions, their expression overlapped. Intense Slick channel immunoreactivity was observed in processes, varicosities, and neuronal cell bodies of the olfactory bulb, granular zones of cortical regions, hippocampus, amygdala, lateral septal nuclei, certain hypothalamic and midbrain nuclei, and several regions of the brainstem. The Slack channel showed primarily a diffuse immunostaining pattern, and labeling of cell somata and processes was observed only occasionally. The highest Slack channel expression was detected in the olfactory bulb, lateral septal nuclei, basal ganglia, and distinct areas of the midbrain, brainstem, and cerebellar cortex. In addition, comparing our data obtained from mouse brain with a previously published study on rat brain revealed some differences in the expression and distribution of Slick and Slack channels in these species. J. Comp. Neurol. 524:2093–2116, 2016. © 2015 The Authors The Journal of Comparative Neurology Published by Wiley Periodicals, Inc.

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Therapeutic Targeting of Potassium Channels

Gamper,

Huang,

et al. 2024

Ion Channels as Targets in Drug Discovery

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Slack and Slick K_Nachannels are required for the depolarizing afterpotential of acutely isolated, medium diameter rat dorsal root ganglion neurons¹

Abstract: We conclude that Slack and Slick K(Na) channels are required for DAP of medium diameter rat DRG neurons that regulate DRG action potential repolarization.

Cited by 30 publications

References 21 publications

NAD⁺Activates K_NaChannels in Dorsal Root Ganglion Neurons

NAD⁺Activates K_NaChannels in Dorsal Root Ganglion Neurons

Differential distribution of the sodium‐activated potassium channels slick and slack in mouse brain

Therapeutic Targeting of Potassium Channels

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Slack and Slick KNachannels are required for the depolarizing afterpotential of acutely isolated, medium diameter rat dorsal root ganglion neurons1

Abstract: We conclude that Slack and Slick K(Na) channels are required for DAP of medium diameter rat DRG neurons that regulate DRG action potential repolarization.

Cited by 30 publications

References 21 publications

NAD+Activates KNaChannels in Dorsal Root Ganglion Neurons

NAD+Activates KNaChannels in Dorsal Root Ganglion Neurons

Differential distribution of the sodium‐activated potassium channels slick and slack in mouse brain

Therapeutic Targeting of Potassium Channels

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Slack and Slick K_Nachannels are required for the depolarizing afterpotential of acutely isolated, medium diameter rat dorsal root ganglion neurons¹

NAD⁺Activates K_NaChannels in Dorsal Root Ganglion Neurons

NAD⁺Activates K_NaChannels in Dorsal Root Ganglion Neurons