ATP-sensitive potassium currents in rat primary afferent neurons: biophysical, pharmacological properties, and alterations by painful nerve injury

Kawano, Takashi; Zoga, V.; McCallum, J. Bruce; Wu, Hsiang‐En; Gemes, Geza; Liang, Mei-Ying; Abram, Stephen E.; Kwok, Wai‐Meng; Hogan, Quinn H.; Sarantopoulos, Constantine

doi:10.1016/j.neuroscience.2009.04.076

Cited by 56 publications

(68 citation statements)

References 32 publications

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“…2؉ currents Whereas activation of inwardly rectifying K ϩ (K IR ) currents appears to be a common mechanism of inhibitory GPCR signaling in CNS neurons and there is evidence that K IR currents are present in nociceptive afferents (Gao et al, 2007;Kawano et al, 2009), there is little direct evidence of Gi-K IR signaling in rodent DRG neurons (McCleskey, 2000). Instead, inhibition of VGCCs (McCleskey, 2000) and AC (Taiwo and Levine, 1991) appears to be the primary mechanisms responsible for the actions of inhibitory GPCR activation.…”

Section: Gi-dreadd Expression Was Associated With Constitutive Ligandmentioning

confidence: 99%

Gi-DREADD Expression in Peripheral Nerves Produces Ligand-Dependent Analgesia, as well as Ligand-Independent Functional Changes in Sensory Neurons

Saloman¹,

Scheff

Snyder³

et al. 2016

J. Neurosci.

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Designer receptors exclusively activated by designer drugs (DREADDs) are an advanced experimental tool that could potentially provide a novel approach to pain management. In particular, expression of an inhibitory (Gi-coupled) DREADD in nociceptors might enable ligand-dependent analgesia. To test this possibility, TRPV1-cre mice were used to restrict expression of Gi-DREADDs to predominantly C-fibers. Whereas baseline heat thresholds in both male and female mice expressing Gi-DREADD were normal, 1 mg/kg clozapine-Noxide (CNO) produced a significant 3 h increase in heat threshold that returned to baseline by 5 h after injection. Consistent with these behavioral results, CNO decreased action potential firing in isolated sensory neurons from Gi-DREADD mice. Unexpectedly, however, the expression of Gi-DREADD in sensory neurons caused significant changes in voltage-gated Ca 2ϩ and Na ϩ currents in the absence of CNO, as well as an increase in Na ϩ channel (NaV1.7) expression. Furthermore, CNO-independent excitatory and inhibitory second-messenger signaling was also altered in these mice, which was associated with a decrease in the analgesic effect of endogenous inhibitory G-proteincoupled receptor activation. These results highlight the potential of this exciting technology, but also its limitations, and that it is essential to identify the underlying mechanisms for any observed behavioral phenotypes.

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Section: Gi-dreadd Expression Was Associated With Constitutive Ligandmentioning

confidence: 99%

Gi-DREADD Expression in Peripheral Nerves Produces Ligand-Dependent Analgesia, as well as Ligand-Independent Functional Changes in Sensory Neurons

Saloman¹,

Scheff

Snyder³

et al. 2016

J. Neurosci.

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“…The primary sensory neuron is known to be an important site of pathogenesis for neuropathic pain, which is a common clinical condition that is difficult to treat by current methods (Amir et al, 2005;Gold, 2000;Zimmermann, 2001). Since our observations also reveal that currents through K ATP channels are significantly decreased by painful nerve injury (Sarantopoulos et al, 2003;Kawano et al, 2009a, 2009c, Zoga et al, 2010, identification of their roles in www.intechopen.com Patch Clamp Technique 74 sensory neurons, particularly regarding excitability, may reveal a contribution to the genesis of neuropathic pain. These researches may lead to development of novel therapies for neuropathic pain.…”

mentioning

confidence: 65%

“…In addition to central nervous systems, we have recently reported that functional K ATP channels are expressed in rat sensory neurons (Kawano et al, 2009a(Kawano et al, , 2009c. The primary sensory neuron is known to be an important site of pathogenesis for neuropathic pain, which is a common clinical condition that is difficult to treat by current methods (Amir et al, 2005;Gold, 2000;Zimmermann, 2001).…”

mentioning

confidence: 99%

“…(Babenko et al, 1998;Miki et al, 1999;Yokoshiki et al, 1998). (Kawano et al, , 2009c In addition to neuronal somata, image analysis results of immunostaining show that K ATP channels are present in glial satellite and Schwann cells (Zoga et al, 2010), which are known to express K + currents (Chiu et al, 1984). K ATP channels in these sites are thought to convey glial cell-mediated clearance of extracellular K + , often termed "K + spatial buffering" (Kofuji et al, 2002).…”

mentioning

confidence: 99%

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Single-Channel Properties and Pharmacological Characteristics of KATP Channels in Primary Afferent Neurons

Kawano¹

2012

Patch Clamp Technique

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“…The administration of xylazine (25,50, and 100 μg) into the right hind paw produced an antinociceptive response against the PGE 2 hyperalgesia (2 μg/paw) in a dose-dependent manner (Fig. 1A), although this was not statistically significant for the dose of 25 μg/paw.…”

Section: Resultsmentioning

confidence: 92%

Involvement of ATP-Sensitive K+ Channels in the Peripheral Antinociceptive Effect Induced by the α2-Adrenoceptor Agonist Xylazine

Romero

Duarte

2009

J Pharmacol Sci

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Abstract. Xylazine is an α 2 -adrenergic agonist extensively used in veterinary medicine and animal experimentation for producing antinociception, sedation, and muscle relaxation. The nitric oxide (NO) / cGMP / ATP-sensitive K + (K ATP ) channel pathway has been proposed as the action mechanism of peripheral antinociception of several groups of drugs, including opioids and nonsteroidal analgesics. Considering the lack of knowledge regarding the mechanisms involved in xylazine effects, the present study investigated the contribution of K + channels on peripheral antinociception induced by xylazine using the rat paw pressure test, in which hyperalgesia was induced by intraplantar injection of prostaglandin E 2 . Xylazine administered into the right hind paw elicited a local antinociceptive effect, since only much higher doses produced a systemic effect in the contralateral paw. The peripheral antinociceptive effect induced by xylazine was antagonized by glibenclamide, a specific blocker of K ATP channels. In another experiment, tetraethylammonium, a voltage-dependent K + -channel blocker, and paxilline and dequalinium, which are selective blockers for the large-and small-conductance Ca 2+ -activated K + channels, respectively, were ineffective at blocking xylazine antinociception. These results provide evidence that the peripheral antinociceptive effect of xylazine probably results from K ATP -channel activation, while the voltage-dependent K + channels, small-and large-conductance Ca 2+-activated K + channels, appear not to be involved in this mechanism.

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ATP-sensitive potassium currents in rat primary afferent neurons: biophysical, pharmacological properties, and alterations by painful nerve injury

Cited by 56 publications

References 32 publications

Gi-DREADD Expression in Peripheral Nerves Produces Ligand-Dependent Analgesia, as well as Ligand-Independent Functional Changes in Sensory Neurons

Gi-DREADD Expression in Peripheral Nerves Produces Ligand-Dependent Analgesia, as well as Ligand-Independent Functional Changes in Sensory Neurons

Single-Channel Properties and Pharmacological Characteristics of KATP Channels in Primary Afferent Neurons

Involvement of ATP-Sensitive K+ Channels in the Peripheral Antinociceptive Effect Induced by the α2-Adrenoceptor Agonist Xylazine

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