INT34425

Context Info Confidence 0.38 First Reported 1987 Last Reported 2010 Negated 1 Speculated 0 Reported most in Body Documents 12 Total Number 12 Disease Relevance 4.17 Pain Relevance 3.20

Anatomy Link Frequency epithelial cells 2 EDL 2 NA (Homo sapiens)

Pain Link Frequency Relevance Heat noradrenaline 8 100.00 Morphine 4 99.66 tetrodotoxin 2 99.36 Action potential 43 99.02 lidocaine 25 97.48 Mexiletine 21 94.72 sodium channel 23 92.24 nMDA receptor antagonist 1 89.84 repetitive firing 2 88.84 antagonist 2 86.00

Disease Link Frequency Relevance Heat Heart Arrhythmia 10 98.44 Congenital Anomalies 6 97.12 Arrhythmia Under Development 2 96.92 Volume Depletion And Dehydration 13 96.56 Sepsis 4 94.24 Hypertension 5 93.48 Hypoxia 130 84.72 Ganglion Cysts 35 83.84 Necrosis 6 82.64 Apoptosis 1 82.12

Sentences Mentioned In

Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

When (+/-)-kavain was dissolved in DMSO, the drug induced a fast and pronounced reduction of both Ca2+ and Na+ currents, which partly recovered within 2-5 min even in the presence of the drug.

Positive_regulation (induced) of Negative_regulation (reduction) of Na

1) Confidence 0.38 Published 1999 Journal Eur Neuropsychopharmacol Section Abstract Doc Link 10082244 Disease Relevance 0.15 Pain Relevance 0.15

The administration of morphine (30 mg/kg i.p.) induced a decrease in the hypothalamic content of NA, with an enhancement in the MHPG and the MHPG/NA ratio.

Positive_regulation (induced) of Negative_regulation (decrease) of NA associated with noradrenaline and morphine

2) Confidence 0.38 Published 1999 Journal Neuropeptides Section Abstract Doc Link 10657482 Disease Relevance 0 Pain Relevance 0.75

CNS-induced suppressions of active Na+, K+ transport was investigated in both 'tonic' muscles, soleus (SOL), and 'twitch' muscle, extensor digitorum longus (EDL) of deoxycorticosterone acetate (DOCA) hypertensive rats.

Positive_regulation (induced) of Negative_regulation (suppressions) of Na in EDL associated with hypertension

3) Confidence 0.32 Published 1987 Journal Brain Res. Section Abstract Doc Link 3036309 Disease Relevance 0.25 Pain Relevance 0.06

However, the N406S mutation in SCN5A causes distinct gating defects and enhanced intermediate inactivation of Na+ channels, which led to unexpected pharmacological effects of lidocaine in a patient carrying this mutation.

Positive_regulation (enhanced) of Negative_regulation (inactivation) of Na associated with lidocaine

4) Confidence 0.30 Published 2007 Journal Int. J. Cardiol. Section Abstract Doc Link 17761312 Disease Relevance 0.71 Pain Relevance 0.50

However, the N406S mutation in SCN5A causes distinct gating defects and enhanced intermediate inactivation of Na+ channels, which led to unexpected pharmacological effects of lidocaine in a patient carrying this mutation.

Positive_regulation (causes) of Negative_regulation (inactivation) of Na associated with lidocaine

5) Confidence 0.30 Published 2007 Journal Int. J. Cardiol. Section Abstract Doc Link 17761312 Disease Relevance 0.72 Pain Relevance 0.50

Simulations suggest both an increase in pacing rate and Na+ channel blockers as beneficial in recovering channel function consistent with the successful arrhythmia management obtained by pacing and high-dose mexiletine.

Positive_regulation (increase) of Negative_regulation (blockers) of Na associated with arrhythmia under development and mexiletine

6) Confidence 0.26 Published 2007 Journal PLoS ONE Section Body Doc Link PMC2082660 Disease Relevance 0.30 Pain Relevance 0.13

Amiloride at 1 mM (Fig. 3A) induced a decrease in total cellular Na+ and K+ levels.

Positive_regulation (induced) of Negative_regulation (decrease) of Na

7) Confidence 0.08 Published 2004 Journal Biol Proced Online Section Body Doc Link PMC443562 Disease Relevance 0 Pain Relevance 0.40

CFTR dysfunction was also induced through Na/K ATPase inhibition by ouabain in airway epithelial cells in another experiment [15].

Positive_regulation (induced) of Negative_regulation (inhibition) of Na in epithelial cells

8) Confidence 0.05 Published 2006 Journal J Inflamm (Lond) Section Body Doc Link PMC1562419 Disease Relevance 0.59 Pain Relevance 0.03

The data presented here show that the inhibition of Gly–Sar uptake by phosphodiesterase inhibitors is both Na+- and pH-dependent (Figs. 1 and 2) suggesting that inhibition is not a direct effect on hPepT1 but rather through NHE3.

Neg (not) Positive_regulation (effect) of Negative_regulation (inhibition) of Na

9) Confidence 0.05 Published 2007 Journal Biochim Biophys Acta Section Body Doc Link PMC2428106 Disease Relevance 0.06 Pain Relevance 0.06

Long-lasting hyperpolarizing potentials were also resistant to blockade of Na+ channels with tetrodotoxin (TTX) (1 µM) (n?

Positive_regulation (resistant) of Negative_regulation (blockade) of Na associated with tetrodotoxin

10) Confidence 0.04 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2637539 Disease Relevance 0 Pain Relevance 0.26

This challenge simulates the effect of a loop diuretic (furosemide) that is known to induce a rapid urinary loss of Na+ and water.

Positive_regulation (induce) of Negative_regulation (loss) of Na

11) Confidence 0.01 Published 2010 Journal BMC Physiol Section Body Doc Link PMC2939538 Disease Relevance 0.35 Pain Relevance 0

However, the reduction of the outward current at potentials > -50 mV contributed mainly to changes in the AP shape und increased after potentials, therefore leading to pronounced inactivation of Na+ currents and reduced firing frequency at higher current stimuli.

Positive_regulation (leading) of Negative_regulation (inactivation) of Na associated with action potential

12) Confidence 0.01 Published 2006 Journal Mol Pain Section Body Doc Link PMC1484470 Disease Relevance 1.03 Pain Relevance 0.37

General Comments

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