INT7458

Context Info Confidence 0.43 First Reported 1990 Last Reported 2011 Negated 0 Speculated 2 Reported most in Abstract Documents 30 Total Number 32 Disease Relevance 6.61 Pain Relevance 10.40

endoplasmic reticulum (Kcnma1) plasma membrane (Kcnma1)

Anatomy Link Frequency neurons 3 outflow 1 brain 1 microglia 1 spinal 1 Kcnma1 (Rattus norvegicus)

Pain Link Frequency Relevance Heat antagonist 52 100.00 sodium channel 9 100.00 Lamotrigine 6 100.00 Calcium channel 5 100.00 Nav1.9 1 99.96 analgesia 3 99.48 hyperexcitability 20 99.40 potassium channel 19 99.36 Neuropeptide 3 99.32 Morphine 133 99.16

Disease Link Frequency Relevance Heat Drug Induced Neurotoxicity 16 99.60 Nociception 26 99.08 Ganglion Cysts 58 98.92 Cv Unclassified Under Development 95 98.90 INFLAMMATION 89 98.84 Cancer Pain 2 98.50 Temporomandibular Joint Syndrome 80 98.32 Neuropathic Pain 67 97.88 Apoptosis 20 95.40 Temporomandibular Joint Disorders 21 95.16

Sentences Mentioned In

Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

We evaluated the effects of iberiotoxin, an inhibitor of Slo-type Ca2+-activated potassium channels and two inhibitors of Shaker-type voltage-gated potassium channels margatoxin and dendrotoxin on acetylcholine outflow in rat striatal slices.

Negative_regulation (inhibitor) of Slo-type in outflow associated with potassium channel

1) Confidence 0.43 Published 1999 Journal Neurosci. Lett. Section Abstract Doc Link 10213172 Disease Relevance 0 Pain Relevance 0.25

Depolarization using 25-100 mM [K+]o resulted in a prompt rise in intracellular calcium concentration, which returned to near resting levels, and this response was sensitive to removal of extracellular calcium and voltage-gated calcium channel antagonists.

Negative_regulation (removal) of channel associated with antagonist and calcium channel

2) Confidence 0.37 Published 1992 Journal Glia Section Abstract Doc Link 1349589 Disease Relevance 0 Pain Relevance 0.41

The mechanism of channel block by amiloride and its analogue seems to be different.

Negative_regulation (block) of channel

3) Confidence 0.37 Published 1994 Journal J. Membr. Biol. Section Abstract Doc Link 8189430 Disease Relevance 0 Pain Relevance 0.16

The channel was blocked by lamotrigine and sipatrigine voltage and state dependently, with potencies 5-20 times higher (IC50 12 and 1.8 microM at -80 mV respectively) than the corresponding block of endogenous Na+ channels from neurones and cloned rNa(v)1.2a (rBIIA) alpha-subunits.

Negative_regulation (blocked) of channel associated with lamotrigine

4) Confidence 0.37 Published 2001 Journal Pflugers Arch. Section Abstract Doc Link 11692262 Disease Relevance 0 Pain Relevance 0.17

CONCLUSION: Our data show that the hypotensive effect induced by TRPV4 activation attributes to, at least in part, activation of MaxiK channels and CGRP receptors upon CGRP release from sensory nerves.

Negative_regulation (activation) of MaxiK in sensory nerves

5) Confidence 0.35 Published 2010 Journal J. Hypertens. Section Body Doc Link 19996988 Disease Relevance 0 Pain Relevance 0

This GS-induced relaxation was partially reversed by tetraethylammonium (TEA), an inhibitor of KCa channels; methylene blue (MB), an inhibitor of soluble guanylate cyclase; as well as Nomega-nitro-L-arginine (L-NNA), but not by glybenclamide.

Negative_regulation (inhibitor) of KCa

6) Confidence 0.34 Published 2001 Journal J. Cardiovasc. Pharmacol. Section Abstract Doc Link 11152372 Disease Relevance 0 Pain Relevance 0

KCNN3 mRNA was prevalent in cultured microglia and increased after lipopolysaccharide-induced activation; SK3 channel blockade inhibited microglial activation and reduced their ability to kill neurons.

Negative_regulation (blockade) of channel in neurons

7) Confidence 0.06 Published 2010 Journal J Neuroinflammation Section Abstract Doc Link PMC2819255 Disease Relevance 0.40 Pain Relevance 0.03

Effects of apamin on microglia are most likely due to SK3 channel block because KCNN2 was nearly undetectable in LPS-activated microglia, and rodent KCNN1 apparently does not form functional channels [44,45].

Negative_regulation (block) of channel in microglia

8) Confidence 0.06 Published 2010 Journal J Neuroinflammation Section Body Doc Link PMC2819255 Disease Relevance 0 Pain Relevance 0

Because one potential outcome of peroxynitrite formation is nitration of cell proteins, we asked whether blocking the SK3 channel in microglia reduces tyrosine nitration in the target neuron cultures.

Spec (whether) Negative_regulation (blocking) of channel in neuron

9) Confidence 0.06 Published 2010 Journal J Neuroinflammation Section Body Doc Link PMC2819255 Disease Relevance 0.21 Pain Relevance 0

Thus, the activation of dorsal horn neurones by nociceptive and non-nociceptive afferent inputs can be differentiated by the blockade of a lamotrigine/flunarizine-sensitive Na+ channel, at a spinal site.

Negative_regulation (blockade) of channel in spinal associated with nociception, lamotrigine and dorsal horn

10) Confidence 0.05 Published 1997 Journal Neuroreport Section Abstract Doc Link 9189890 Disease Relevance 0.20 Pain Relevance 0.30

PTX-induced analgesia was blocked by selective inhibitors of nitric oxide synthase (L-NMMA), guanylyl cyclase (ODQ), protein kinase G (KT5823) and ATP-sensitive K(+) channel (Kir6) blockers (glybenclamide and tolbutamide).

Negative_regulation (inhibitors) of channel associated with analgesia

11) Confidence 0.03 Published 2006 Journal Eur. J. Neurosci. Section Abstract Doc Link 16930443 Disease Relevance 0.21 Pain Relevance 0.21

Similarly, axotomy reduces KCa channel activity in the small to medium sized DRG neurons, which would also increase membrane excitability [21].

Negative_regulation (reduces) of KCa in neurons associated with dorsal root ganglion

12) Confidence 0.03 Published 2011 Journal Mol Pain Section Body Doc Link PMC3024960 Disease Relevance 1.71 Pain Relevance 1.58

Glycosylation alters steady-state inactivation of sodium channel Nav1.9/NaN in dorsal root ganglion neurons and is developmentally regulated.

Negative_regulation (inactivation) of channel in dorsal root ganglion associated with ganglion cysts, neuropeptide, root ganglion neuron, sodium channel and nav1.9

13) Confidence 0.02 Published 2001 Journal J. Neurosci. Section Title Doc Link 11739573 Disease Relevance 0.10 Pain Relevance 0.30

It is concluded that protection against veratridine-induced neurotoxicity can be mediated by blocking a veratridine-sensitive Na+ channel.

Negative_regulation (blocking) of channel associated with drug induced neurotoxicity

14) Confidence 0.02 Published 1990 Journal J. Pharmacol. Exp. Ther. Section Abstract Doc Link 2175795 Disease Relevance 0.10 Pain Relevance 0.40

We applied paxilline during the preconditioning period, suggesting that mKCa channel inhibition blocks the infarct size reducing effect of preconditioning during the trigger phase.

Negative_regulation (inhibition) of channel

15) Confidence 0.02 Published 2010 Journal Can J Anaesth Section Body Doc Link PMC2899019 Disease Relevance 0.10 Pain Relevance 0.22

To test whether mKCa channels are involved in the phenomenon of preconditioning, the mKCa channel inhibitor, paxilline 1 ?

Negative_regulation (inhibitor) of channel

16) Confidence 0.02 Published 2010 Journal Can J Anaesth Section Body Doc Link PMC2899019 Disease Relevance 0.57 Pain Relevance 0.80

The preconditioning effect of ischemia and morphine was attenuated significantly by the mKCa-channel inhibitor, paxilline.

Negative_regulation (inhibitor) of channel associated with ischemia and morphine

17) Confidence 0.02 Published 2010 Journal Can J Anaesth Section Body Doc Link PMC2899019 Disease Relevance 0.26 Pain Relevance 0.35

These disorders are currently managed by drugs that are dampen neuronal hyperexcitability through voltage-gated sodium channel inhibition, modulation of voltage-gated calcium channels and their auxiliary subunits, and inhibitory GABAergic neurotransmission [6].

Negative_regulation (inhibition) of channel in neuronal associated with gabaergic, calcium channel, sodium channel and hyperexcitability

18) Confidence 0.02 Published 2010 Journal Mol Pain Section Body Doc Link PMC2936374 Disease Relevance 1.43 Pain Relevance 1.89

In this study, we sought to elucidate the molecular mechanisms underlying Rg(3)-induced Na(+) channel inhibition.

Negative_regulation (inhibition) of channel

19) Confidence 0.02 Published 2005 Journal Mol. Pharmacol. Section Abstract Doc Link 16014805 Disease Relevance 0 Pain Relevance 0.23

These results reveal that Rg(3) is a novel Na(+) channel inhibitor capable of acting on the resting and open states of Na(+) channel via interactions with the S4 voltage-sensor segment of domain II.

Negative_regulation (inhibitor) of channel

20) Confidence 0.02 Published 2005 Journal Mol. Pharmacol. Section Abstract Doc Link 16014805 Disease Relevance 0 Pain Relevance 0.33

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