A mutation in the local anaesthetic binding site abolishes toluene effects in sodium channels

Gauthereau, Marcia Yvette; Salinas-Stefanon, Eduardo M.; Cruz, Silvia L.

doi:10.1016/j.ejphar.2005.10.069

Cited by 18 publications

(7 citation statements)

References 31 publications

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“…Other studies with other mammalian sodium channels and other LA drugs showed reductions in open and inactivated channel block, with slight variations occurring according to which LA was used (Gauthereau et al, 2005; Li et al, 1999; Liu et al, 2003; Ragsdale et al, 1994; Ragsdale et al, 1996; Wang et al, 2004; Weiser et al, 1999; Wright et al, 1998). Thus, our results indicate that the residues F1817 and Y1824 of IVS6 in cockroach sodium channels are required for mediating the interaction between lidocaine and open or inactivated, but not resting, channel states in a manner similar to mammalian sodium channels.…”

Section: Discussionmentioning

confidence: 97%

“…Two specific residues in IVS6 of mammalian sodium channels, F1764 and Y1771 in rat Na v 1.2 sodium channels and F1579 and Y1586 in Na v 1.4 sodium channels, are required for the action of LAs on mammalian sodium channels (Gauthereau et al, 2005; Li et al, 1999; Liu et al, 2003; Ragsdale et al, 1994; Ragsdale et al, 1996; Wang et al, 2004; Weiser et al, 1999; Wright et al, 1998). We show here that the corresponding residues in the cockroach sodium channel also contribute to the action of lidocaine on insect sodium channels.…”

Section: Discussionmentioning

confidence: 99%

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Analysis of the action of lidocaine on insect sodium channels

Song

Silver

et al. 2011

Insect Biochemistry and Molecular Biology

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A new class of sodium channel blocker insecticides (SCBIs), which include indoxacarb, its active metabolite, DCJW, and metaflumizone, preferably block inactivated states of both insect and mammalian sodium channels in a manner similar to that by which local anesthetic (LA) drugs block mammalian sodium channels. A recent study showed that two residues in the cockroach sodium channel, F1817 and Y1824, corresponding to two key LA-interacting residues identified in mammalian sodium channels are not important for the action of SCBIs on insect sodium channels, suggesting unique interactions of SCBIs with insect sodium channels. However, the mechanism of action of LAs on insect sodium channels has not been investigated. In this study, we examined the effects of lidocaine on a cockroach sodium channel variant, BgNa v 1-1a, and determined whether F1817 and Y1824 are also critical for the action of LAs on insect sodium channels. Lidocaine blocked BgNa v 1-1a channels in the resting state with potency similar to that observed in mammalian sodium channels. Lidocaine also stabilized both fast-inactivated and slow-inactivated states of BgNa v 1-1a channels, and caused a limited degree of use-and frequency-dependent block, major characteristics of LA action on mammalian sodium channels. Alanine substitutions of F1817 and Y1824 reduced the sensitivity of the BgNa v 1-1a channel to the use-dependent block by lidocaine, but not to tonic blocking and inactivation stabilizing effects of lidocaine. Thus, similar to those on mammalian sodium channels, F1817 and Y1824 are important for the action of lidocaine on cockroach sodium channels. Our results suggest that the receptor sites for lidocaine and SCBIs are different on insect sodium channels.

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Analysis of the action of lidocaine on insect sodium channels

Song

Silver

et al. 2011

Insect Biochemistry and Molecular Biology

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“…On the other hand, ethanol, anesthetics, toluene, TCE, and tetrachloroethylene, also known as perchloroethylene (PERC), all inhibit voltage-sensitive calcium current-mediated voltage-gated calcium channels (Shafer et al, 2005;Tillar et al, 2002). Toluene also inhibits voltage-gated sodium channels, with cardiac subtypes being more sensitive than those expressed in neurons (Cruz et al, 2003;Gauthereau et al, 2005). This mechanism may relate to an abuser's development of 'Sudden Sniffing Death Syndrome,' which is a form of cardiac failure resulting from acute, high concentration exposure to volatile solvents (Kurtzman et al, 2001).…”

Section: Pharmacologymentioning

confidence: 99%

Volatile Solvents as Drugs of Abuse: Focus on the Cortico-Mesolimbic Circuitry

Beckley

Woodward

2013

Neuropsychopharmacol

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Volatile solvents such as those found in fuels, paints, and thinners are found throughout the world and are used in a variety of industrial applications. However, these compounds are also often intentionally inhaled at high concentrations to produce intoxication. While solvent use has been recognized as a potential drug problem for many years, research on the sites and mechanisms of action of these compounds lags behind that of other drugs of abuse. In this review, we first discuss the epidemiology of voluntary solvent use throughout the world and then consider what is known about their basic pharmacology and how this may explain their use as drugs of abuse. We next present data from preclinical and clinical studies indicating that these substances induce common addiction sequelae such as dependence, withdrawal, and cognitive impairments. We describe how toluene, the most commonly studied psychoactive volatile solvent, alters synaptic transmission in key brain circuits such as the mesolimbic dopamine system and medial prefrontal cortex (mPFC) that are thought to underlie addiction pathology. Finally, we make the case that activity in mPFC circuits is a critical regulator of the mesolimbic dopamine system's ability to respond to volatile solvents like toluene. Overall, this review provides evidence that volatile solvents have high abuse liability because of their selective effects on critical nodes of the addiction neurocircuitry, and underscores the need for more research into how these compounds induce adaptations in neural circuits that underlie addiction pathology.

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“…Toluene concentration dependently inhibits sodium channels, which are responsible for the initial depolarizing phase of cardiac action potential (Cruz et al, 2003), an effect that could be related with toluene's arrhythmogenic actions. Interestingly, a single mutation on the local anesthetics binding site is enough to abolish the inhibitory effects of this solvent, suggesting that toluene has affinity for this site (Gauthereau et al, 2005;Scior et al, 2009). Toluene inhibits dihydropyridinesensitive and -insensitive calcium channels (Tillar et al, 2002), which is also observed with other halogenated hydrocarbons (trichloroethylene and perchloroethylene) using different experimental preparations (Shafer et al, 2005).…”

Section: Solventsmentioning

confidence: 96%