Differential effects of the pyrethroid tetramethrin on tetrodotoxin-sensitive and tetrodotoxin-resistant single sodium channels

Song, Jin-Ho; Narahashi, Toshio

doi:10.1016/0006-8993(95)01449-7

Cited by 123 publications

(141 citation statements)

References 15 publications

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“…To estimate the affinity of riluzole for binding to inactivated Na ϩ channels in the preBötC region, the apparent dissociation constant (K i ) was calculated (see Materials and Methods). The K i value of 0.3 Ϯ 0.1 M (n ϭ 9) indicated an approximately eightfold greater apparent affinity of riluzole compared with the EC 50 value, consistent with a highly preferential block of Na ϩ channels in the inactivated state, as reported previously (Benoit and Escande, 1991;Hebert et al, 1994;Song et al, 1997;Urbani and Belluzzi, 2000). As a result, the effect of riluzole on Na ϩ current would be expected to depend on the holding potential of a neuron.…”

Section: Mechanism Of Nasupporting

confidence: 83%

“…One study has reported riluzole-induced shortening of the inactivation time constant of Na ϩ current (Song et al, 1997), whereas others have reported no effect (Benoit and Escande, 1991;Hebert et al, 1994). Faster inactivation in the presence of riluzole would decrease the availability of Na ϩ channels for inactivation during step depolarizations.…”

Section: Mechanism Of Namentioning

confidence: 99%

“…؉ channel modulation by riluzole A variety of investigators (Benoit and Escande, 1991;Hebert et al, 1994;Song et al, 1997;Urbani and Belluzzi, 2000) have interpreted the effects of riluzole on Na ϩ channels according to a modulated receptor model (Hille, 1977). In this model, the affinity of the drug for Na ϩ channels depends on the gating state (deinactivated, open, or inactivated).…”

Section: Mechanism Of Namentioning

confidence: 99%

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Sodium Currents in Medullary Neurons Isolated from the Pre-Bötzinger Complex Region

Ptak

Zummo²,

Alheid³

et al. 2005

J. Neurosci.

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The pre-Bötzinger complex (preBötC) in the ventrolateral medulla contains interneurons important for respiratory rhythm generation. Voltage-dependent sodium channels mediate transient current (I NaT ), underlying action potentials, and persistent current (I NaP ), contributing to repetitive firing, pacemaker properties, and the amplification of synaptic inputs. Voltage-clamp studies of the biophysical properties of these sodium currents were conducted on acutely dissociated preBötC region neurons. Reverse transcription-PCR demonstrated the presence of mRNA for Nav1.1, Nav1.2, and Nav1.6 ␣-subunits in individual neurons. A TTX-sensitive I NaP was evoked in all tested neurons by ramp depolarization from Ϫ80 to 0 mV. Including a constant in the Boltzmann equation for inactivation by estimating the steady-state fraction of Na ϩ channels available for inactivation allowed prediction of a window current that did not decay to 0 at voltages positive to Ϫ20 mV and closely matched the measured I NaP . Riluzole (3 M), a putative I NaP antagonist, reduced both I NaP and I NaT and produced a hyperpolarizing shift in the voltage dependence of steady-state inactivation. The latter decreased the predicted window current by an amount equivalent to the decrease in I NaP . Riluzole also decreased the inactivation time constant at potentials in which the peak window/persistent currents are generated. Together, these findings imply that I NaP and I NaT arise from the same channels and that a simple modification of the Hodgkin-Huxley model can satisfactorily account for both currents. In the rostral ventral respiratory group (immediately caudal to preBötC), I NaP was also detected, but peak conductance, current density, and input resistance were smaller than in preBötC region cells.

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Section: Mechanism Of Nasupporting

confidence: 83%

Section: Mechanism Of Namentioning

confidence: 99%

Section: Mechanism Of Namentioning

confidence: 99%

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Sodium Currents in Medullary Neurons Isolated from the Pre-Bötzinger Complex Region

Ptak

Zummo²,

Alheid³

et al. 2005

J. Neurosci.

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“…Currently, the only FDA-approved, disease-modifying drug used for the treatment of ALS is riluzole, which inhibits neuronal glutamate, releases and stimulates glutamate uptake into astrocytes. 2 The use of riluzole is based on the hypothesis that overactivation of Ca 2 þ -permeable AMPA receptors in motoneurons results in excitotoxicity, and that this process contributes to motoneuron death in ALS. 3 Nevertheless, the disease-modifying effects of riluzole therapy are moderate and vary among patients.…”

mentioning

confidence: 99%

Acidotoxicity and acid-sensing ion channels contribute to motoneuron degeneration

et al. 2013

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Amyotrophic lateral sclerosis (ALS) is a fatal neurological condition with no cure. Mitochondrial dysfunction, Ca 2 þ overloading and local hypoxic/ischemic environments have been implicated in the pathophysiology of ALS and are conditions that may initiate metabolic acidosis in the affected tissue. We tested the hypothesis that acidotoxicity and acid-sensing ion channels (ASICs) are involved in the pathophysiology of ALS. We found that motoneurons were selectively vulnerable to acidotoxicity in vitro, and that acidotoxicity was partially reduced in asic1a-deficient motoneuron cultures. Cross-breeding of SOD1 G93A ALS mice with asic1a-deficient mice delayed the onset and progression of motor dysfunction in SOD1 mice. Interestingly, we also noted a strong increase in ASIC2 expression in motoneurons of SOD1 mice and sporadic ALS patients during disease progression. Pharmacological pan-inhibition of ASIC channels with the lipophilic amiloride derivative, 5-(N,N-dimethyl)-amiloride hydrochloride, potently protected cultured motoneurons against acidotoxicity, and, given post-symptom onset, significantly improved lifespan, motor performance and motoneuron survival in SOD1 mice. Together, our data provide strong evidence for the involvement of acidotoxicity and ASIC channels in motoneuron degeneration, and highlight the potential of ASIC inhibitors as a new treatment approach for ALS. Cell Death and Differentiation (2013) 20, 589-598; doi:10.1038/cdd.2012.158; published online 11 January 2013Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative condition where motoneurons in the spinal cord and brain stem die, resulting in paralysis and eventual death. Despite the significant recent advances in understanding the pathophysiology and genetics of ALS, 1 there is no cure for this condition. Currently, the only FDA-approved, disease-modifying drug used for the treatment of ALS is riluzole, which inhibits neuronal glutamate, releases and stimulates glutamate uptake into astrocytes. 2 The use of riluzole is based on the hypothesis that overactivation of Ca 2 þ -permeable AMPA receptors in motoneurons results in excitotoxicity, and that this process contributes to motoneuron death in ALS. 3 Nevertheless, the disease-modifying effects of riluzole therapy are moderate and vary among patients. 4 Acid-sensing ion channels (ASICs) represent a group of ion channels activated by protons. They belong to the epithelial sodium (Na þ ) family of amiloride-sensitive cation channels, and allow for Na þ and Ca 2 þ entry into neurons. Of the six ASIC subunits cloned, ASIC1a, ASIC2a and ASIC2b are expressed in the brain and spinal cord neurons. 5 ASIC1a and ASIC2s are found in the brain regions with high synaptic density and facilitate excitatory synaptic transmission. 6,7 ASIC1a in particular is involved in nociception and fear behavior triggered by hypercapnia. 8,9 ASICs have also been investigated as new targets for the treatment of ischemic stroke and cerebral hypoxia 10 on the premise that activation of ASIC1a during ischemia ...

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“…7 Moreover, they are also used as drugs for treatment of diabetes. 8 Benzothiazole unit is found in zopolrestat 9 and riluzole, 10 which are used to treat diabetes.…”

Section: Introductionmentioning

confidence: 99%

Lanthanum (III) nitrate hexahydrate catalyzed one-pot synthesis of 2-arylbenzothiazoles under mild reaction conditions

Shaikh¹,

Chaudhar²

2017

Org.Commun.

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Differential effects of the pyrethroid tetramethrin on tetrodotoxin-sensitive and tetrodotoxin-resistant single sodium channels

Cited by 123 publications

References 15 publications

Sodium Currents in Medullary Neurons Isolated from the Pre-Bötzinger Complex Region

Sodium Currents in Medullary Neurons Isolated from the Pre-Bötzinger Complex Region

Acidotoxicity and acid-sensing ion channels contribute to motoneuron degeneration

Lanthanum (III) nitrate hexahydrate catalyzed one-pot synthesis of 2-arylbenzothiazoles under mild reaction conditions

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