INT13118

Context Info Confidence 0.69 First Reported 1988 Last Reported 2010 Negated 0 Speculated 1 Reported most in Abstract Documents 48 Total Number 50 Disease Relevance 7.39 Pain Relevance 13.85

cell differentiation (Ina) structural molecule activity (Ina)

Anatomy Link Frequency neurons 4 myocytes 3 heart 2 BFA 1 nociceptors 1 Ina (Rattus norvegicus)

Pain Link Frequency Relevance Heat tetrodotoxin 353 100.00 addiction 29 99.92 Kinase C 22 99.84 lidocaine 9 99.30 ischemia 37 99.24 inferior alveolar nerve 604 98.92 Endep 6 98.88 trigeminal ganglion 264 98.32 Action potential 289 97.04 hyperexcitability 32 96.52

Disease Link Frequency Relevance Heat Heart Rate Under Development 48 99.60 Cv Unclassified Under Development 72 99.24 Coronary Heart Disease 6 99.08 Ganglion Cysts 295 98.32 Hyperalgesia 3 96.88 Fatigue 1 95.32 Pituitary Cancer 5 92.40 Coronary Artery Disease 1 92.20 Depression 8 91.88 Diastolic Heart Failure 5 91.80

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Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

As indicated by slow depolarizing voltage ramps, activation of INaP did not require preceding activation of the fast, rapidly inactivating Na+ current. 3.

Positive_regulation (activation) of INaP

1) Confidence 0.69 Published 1995 Journal J. Neurophysiol. Section Abstract Doc Link 7500162 Disease Relevance 0 Pain Relevance 0.34

In the recent years, increased late INa was suggested to contribute to this phenomenon by elevating intracellular Na concentration with subsequent rise in diastolic Ca levels by means of the sarcolemmal Na-Ca exchange system.

Positive_regulation (increased) of INa

2) Confidence 0.60 Published 2009 Journal J. Cardiovasc. Pharmacol. Section Abstract Doc Link 19333133 Disease Relevance 0.55 Pain Relevance 0.38

High concentrations of QDs post-poned activation of INa (Figure 5B) at the command voltage of ?

Positive_regulation (activation) of INa

3) Confidence 0.47 Published 2008 Journal Environ Health Perspect Section Body Doc Link PMC2453160 Disease Relevance 0 Pain Relevance 0

INa activated close to -60 mV, showed fast time- and voltage-dependent activation and inactivation, and was completely, and reversibly, blocked by submicromolar concentrations of tetrodotoxin (Kd = 17 nM).

Positive_regulation (activated) of INa associated with tetrodotoxin

4) Confidence 0.46 Published 2003 Journal J. Neurophysiol. Section Abstract Doc Link 12702715 Disease Relevance 0 Pain Relevance 0.09

This behavior is not consistent with the notion that INaP arises solely from a bell-shaped window conductance that results from the overlapping steady-state activation and inactivation curves of the fast Na+ current in a narrow voltage range, nor with the notion that INaP is generated by a single uniform conductance independent of the fast Na+ current. 5.

Positive_regulation (generated) of INaP

5) Confidence 0.46 Published 1995 Journal J. Neurophysiol. Section Abstract Doc Link 7500162 Disease Relevance 0 Pain Relevance 0.29

These data suggest that the increase in both TTX-S INa and TTX-R INa and the decrease in IA and Ik in small/medium TG neurons in IAN-transected rats are involved in the activation of spike generation, resulting in hyperexcitability of A?

Positive_regulation (increase) of INa in neurons associated with tetrodotoxin, inferior alveolar nerve, trigeminal ganglion and hyperexcitability

6) Confidence 0.46 Published 2010 Journal Mol Pain Section Abstract Doc Link PMC2829527 Disease Relevance 0.45 Pain Relevance 1.38

These data suggest that the increase in both TTX-S INa and TTX-R INa and the decrease in IA and Ik in small/medium TG neurons in IAN-transected rats are involved in the activation of spike generation, resulting in hyperexcitability of A?

Positive_regulation (increase) of INa in neurons associated with tetrodotoxin, inferior alveolar nerve, trigeminal ganglion and hyperexcitability

7) Confidence 0.46 Published 2010 Journal Mol Pain Section Abstract Doc Link PMC2829527 Disease Relevance 0.45 Pain Relevance 1.38

These data are consistent with voltage escape during activation of INa leading to a trigger Ca entry via a mechanism other than L-type Ca channels or subsarcolemmal Na accumulation with reverse Na-Ca exchange.

Positive_regulation (activation) of INa

8) Confidence 0.45 Published 1995 Journal Pflugers Arch. Section Abstract Doc Link 8594540 Disease Relevance 0 Pain Relevance 0.31

Activation of INaP did not require preceding activation of the transient Na+ current. 3.

Positive_regulation (Activation) of INaP

9) Confidence 0.45 Published 1993 Journal J. Neurophysiol. Section Abstract Doc Link 8381860 Disease Relevance 0 Pain Relevance 0.17

While the voltage dependence of INa activation and steady-state inactivation were constant from cell to cell, the time course of recovery was not.

Positive_regulation (activation) of INa associated with addiction

10) Confidence 0.41 Published 1991 Journal Neurosci. Res. Section Abstract Doc Link 1661876 Disease Relevance 0.21 Pain Relevance 0.13

The most marked increase of the maximal available INa+ was 30+/-9% after application of 100 nmol/l isoproterenol.

Positive_regulation (increase) of INa

11) Confidence 0.41 Published 1996 Journal Pflugers Arch. Section Abstract Doc Link 8584433 Disease Relevance 0 Pain Relevance 0.22

Although the increase in the magnitude of TTX-S INa was larger than that of TTX-R INa in the TG neurons after IAN transection, it is possible that the hyperexcitability of TG neurons innervated by the regenerated IAN is augmented by an increase in TTX-R Na+ current densities, resulting in abnormal excitation of the CNS networks and nociceptive behavior.

Positive_regulation (increase) of INa in neurons associated with nociception, tetrodotoxin, inferior alveolar nerve, trigeminal ganglion, central nervous system and hyperexcitability

12) Confidence 0.40 Published 2010 Journal Mol Pain Section Body Doc Link PMC2829527 Disease Relevance 1.07 Pain Relevance 1.58

In addition to increase in INa, we can raise the possibility that the reduction of both IK and IA contributes to the hyperexcitability of IAN-transected TG neurons.

Positive_regulation (increase) of INa in neurons associated with inferior alveolar nerve, trigeminal ganglion and hyperexcitability

13) Confidence 0.40 Published 2010 Journal Mol Pain Section Body Doc Link PMC2829527 Disease Relevance 0.81 Pain Relevance 1.01

The sodium current (INa) was activated by depolarization of beyond -45 mV and was maximal (approximately 60 pA) at -10 mV.

Positive_regulation (activated) of INa

14) Confidence 0.40 Published 1988 Journal J. Neurophysiol. Section Abstract Doc Link 3351572 Disease Relevance 0 Pain Relevance 0.09

During voltage-clamp in the whole-cell mode, depolarizing voltage steps activated Na(+)-(INa), Ca(2+)-(ICa), and K(+)-currents in all cells tested (n = 122).

Positive_regulation (activated) of INa

15) Confidence 0.40 Published 1991 Journal Neuroscience Section Abstract Doc Link 1717883 Disease Relevance 0.50 Pain Relevance 0.14

For amiodarone and lidocaine, the inhibition was observed when INa was elicited from a holding potential of -70 mV.

Positive_regulation (elicited) of INa associated with lidocaine

16) Confidence 0.40 Published 1990 Journal Proc. Natl. Sci. Counc. Repub. China B Section Abstract Doc Link 1701057 Disease Relevance 0 Pain Relevance 0.57

CN caused little or no change in INa activation, fast inactivation, recovery from inactivation, or current-voltage (I-V) relationship. 7.

Positive_regulation (activation) of INa

17) Confidence 0.37 Published 1991 Journal J. Neurophysiol. Section Abstract Doc Link 1662712 Disease Relevance 0.24 Pain Relevance 0.12

INa was activated by depolarization of the cell from the holding potential (Vh) of -95 mV to membrane voltages (Vm) more positive than -45 mV.

Positive_regulation (activated) of INa

18) Confidence 0.36 Published 1991 Journal Neurosci. Res. Section Abstract Doc Link 1661876 Disease Relevance 0.32 Pain Relevance 0.13

The values of V1/2, at which the conductance of INa reaches half of its maximum, were shifted from ?

Positive_regulation (conductance) of INa

19) Confidence 0.34 Published 2008 Journal Environ Health Perspect Section Body Doc Link PMC2453160 Disease Relevance 0 Pain Relevance 0.19

INaP was activated positive to about -60 mV and attained its peak amplitude between -40 and -35 mV.

Positive_regulation (activated) of INaP

20) Confidence 0.32 Published 1993 Journal J. Neurophysiol. Section Abstract Doc Link 8381860 Disease Relevance 0 Pain Relevance 0.18

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