Effect of curare on responses to different putative neurotransmitters in <i>Aplysia</i> neurons

Carpenter, David O.; Swann, John W.; Yarowsky, PJ

doi:10.1002/neu.480080204

Cited by 101 publications

(30 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For example, [smcap]d-tubocurarine acts also on GABA and on 5HT receptors (30,31); dopamine activates 5HT 1c and 5HT 2 receptors (32); glycine activates GABA receptors (33); and many serotonergic compounds interfere with AcChoRs (16,22,29,(34)(35)(36). Strychnine acts as antagonist of glycine, GABA A , and nicotinic receptors probably because they show high structural similarities (37,38).…”

Section: Discussionmentioning

confidence: 99%

Modulation of nicotinic acetylcholine receptors by strychnine

Garcı́a-Colunga

Miledi²

1999

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Strychnine, a potent and selective antagonist at glycine receptors, was found to inhibit muscle (␣ 1 ␤ 1 ␥␦, ␣ 1 ␤ 1 ␥, and ␣ 1 ␤ 1 ␦) and neuronal (␣ 2 ␤ 2 and ␣ 2 ␤ 4 ) nicotinic acetylcholine receptors (AcChoRs) expressed in Xenopus oocytes. Strychnine alone (up to 500 M) did not elicit membrane currents in oocytes expressing AcChoRs, but, when applied before, concomitantly, or during superfusion of acetylcholine (AcCho), it rapidly and reversibly inhibited the current elicited by AcCho (AcCho-current). Although in the three cases the AcCho-current was reduced to the same level, its recovery was slower when the oocytes were preincubated with strychnine. The amount of AcCho-current inhibition depended on the receptor subtype, and the order of blocking potency by strychnine was ␣ 1 ␤ 1 ␥␦ > ␣ 2 ␤ 4 > ␣ 2 ␤ 2 . With the three forms of drug application, the Hill coefficient was close to one, suggesting a single site for the receptor interaction with strychnine, and this interaction appears to be noncompetitive. The inhibitory effects on muscle AcChoRs were voltageindependent, and the apparent dissociation constant for AcCho was not appreciably changed by strychnine. In contrast, the inhibitory effects on neuronal AcChoRs were voltagedependent, with an electrical distance of Ϸ0.35. We conclude that strychnine regulates reversibly and noncompetitively the embryonic type of muscle AcChoR and some forms of neuronal AcChoRs. In the former case, strychnine presumably inhibits allosterically the receptor by binding at an external domain whereas, in the latter case, it blocks the open receptorchannel complex.Nicotinic acetylcholine receptors (AcChoRs) are members of a gene superfamily that includes GABA A , glycine, and 5HT 3 receptors (1). They are activated by the neurotransmitter acetylcholine (AcCho), and they mediate fast synaptic transmission at the neuromuscular junction and throughout the vertebrate nervous system (2-4). Additionally, AcChoRs are regulated by a wide variety of substances (5, 6), including strychnine, a selective antagonist of glycine-gated Cl Ϫ channels (7) that inhibits AcChoRs at the neuromuscular junction (8) and different types of neurons (9-13). Moreover, it appears that this inhibition depends on the subtype of nicotinic receptor involved. For instance, in bovine adrenal chromaffin cells and rat hippocampal neurons, strychnine inhibits AcChoRs competitively whereas for ␣ 4 ␤ 2 -containing AcChoRs the inhibition is noncompetitive (10, 13). Here, we report the effects of strychnine on muscle AcChoRs made up of ␣ 1 ␤ 1 ␥␦, ␣ 1 ␤ 1 ␥, or ␣ 1 ␤ 1 ␦ muscle subunits and on two subtypes of neuronal AcChoRs (␣ 2 ␤ 2 or ␣ 2 ␤ 4 ). MATERIALS AND METHODSThe methods were as previously described (14-16). In brief, cDNA clones encoding embryonic mouse muscle AcChoR subunits (␣ 1 , ␤ 1 , ␥, and ␦) or rat neuronal AcChoR subunits (␣ 2 , ␤ 2 , or ␤ 4 ) were used to make cRNAs that were suspended in RNase-free water at a concentration of 1 g͞l. Mixtures then were made with equal quantities of the requ...

show abstract

Section: Discussionmentioning

confidence: 99%

Modulation of nicotinic acetylcholine receptors by strychnine

Garcı́a-Colunga

Miledi²

1999

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…They render unlikely the involvement of nonspecific effects of d-TC (Nohmi and Kuba, 1984;Capiod and Ogden, 1989). It should be noted, however, that because d-TC has been previously shown to block Cll channels activated by the iontophoretic application oftransmitters other than ACh in the CNS ofAplysia (Carpenter et al, 1977), one cannot be absolutely sure that ACh is the transmitter at all inhibitory synapses of the GSWR network. It is, however, likely that ACh is the transmitter because (1) most described fast inhibitory synaptic action in the CNS of Aplysia is known to be cholinergic (this is the case, e.g., at all fast inhibitory synapses that have been characterized in the buccal ganglion), (2) the excitatory intemeurons of the GSWR network respond to the iontophoretic application of ACh by the opening of Cll channels, (3) biochemical evidence (Giller and Schwartz, 1971) has indicated that there are significant levels of ChAT activity in the section of the abdominal ganglion where we have located (L.-E. Trudeau and V. F. Castellucci, unpublished ob-servations) most of the inhibitory intemeurons of the GSWR, and (4) inhibitory intemeuron L16, which is part of the GSWR network, has been demonstrated to be cholinergic (Segal and Koester, 1982).…”

Section: Discussionmentioning

confidence: 99%

Functional uncoupling of inhibitory interneurons plays an important role in short-term sensitization of Aplysia gill and siphon withdrawal reflex

Trudeau

Castellucci

1993

J. Neurosci.

View full text Add to dashboard Cite

Attempts to explain learning-associated potentiation of synaptic transmission in model systems such as withdrawal reflexes in the mollusk Aplysia or the hippocampus of vertebrates have focused on the mechanisms by which transmitter release is increased in the principal elements of the circuit. Increased transmission in neuronal networks such as the gill and siphon withdrawal reflex (GSWR) of Aplysia may, however, also be caused by a decrease of transmitter release by inhibitory interneurons. The importance and function of cholinergic inhibitory transmission in the GSWR network were investigated. Central application of the nicotinic cholinergic antagonist d-tubocurarine (d- TC) considerably potentiated gill contractions, evoked either by nerve stimulation or by tactile stimulation of the siphon. Compound EPSPs evoked in motoneurons upon siphon nerve stimulation were also significantly prolonged following application of d-TC, but were unaffected by hexamethonium, a blocker of excitatory ACh receptors in Aplysia. Recordings from excitatory interneurons showed that they received excitation followed by powerful inhibitory input upon stimulation of the siphon nerve. Application of d-TC completely blocked this rapid inhibition, thus prolonging the compound EPSPs evoked in the interneurons. These effects were obtained at a concentration of d-TC (100 microM) that almost totally blocked fast inhibitory cholinergic transmission, but was without effect on monosynaptic connections between sensory neurons and motoneurons of the reflex. Facilitation of (1) compound EPSCs in motoneurons and (2) evoked excitatory interneuronal firing was reduced in preparations already disinhibited by pretreatment with d-TC. Facilitation of sensory-motor synapses, however, was not reduced in the presence of d-TC, indicating that facilitatory interneurons are still activated under cholinergic blockade. These data show that transmission through the GSWR neuronal network is gated by a feedback inhibitory mechanism. They also suggest that a reduction of cholinergic inhibition onto excitatory interneurons may be a mechanism through which transmission within the GSWR network is increased during various forms of learning, such as sensitization. These data place new emphasis on the important role of inhibitory interneurons in determining the plastic properties of neuronal networks, in both invertebrates and vertebrates.

show abstract

“…As produce a voltage-independent block of 5-HT3-mediated currents (Peters et al, 1988;Lovinger, 1991 (Ascher, 1972;Carpenter et al, 1977).…”

Section: S-ht Responses In E4 Es and E6mentioning

confidence: 99%

Ligand‐gated ion channels opened by 5‐HT in molluscan neurones

Green

Lambert

Cottrell

1996

British J Pharmacology

View full text Add to dashboard Cite

1 5-Hydroxytryptamine (5-HT) activated a fast (70 ms to half maximum) and desensitizing inward current through non-selective channels conducting predominantly monovalent cations in neurones of Helix aspersa.2 a-Methyl-5-HT was equipotent with 5-HT in activating this current, but the known selective agonists at vertebrate 5-HT3 receptors, 2-methyl-5-HT and arylbiguanides were ineffective (< 100 gM). 5-Methoxytryptamine which is inactive on vertebrate 5-HT3 receptors was a very weak agonist. 3 The responses were antagonized by the specific vertebrate 5-HT3 receptor blocker MDL-72222 (IC50 = 1 gM), but were only weakly affected by ondansetron (10 gM). The 5-HT2-type antagonist, ketanserin (<5 gM), had no effect. The responses were also antagonized by the non-specific antagonists

show abstract

Effect of curare on responses to different putative neurotransmitters in Aplysia neurons

Cited by 101 publications

References 27 publications

Modulation of nicotinic acetylcholine receptors by strychnine

Modulation of nicotinic acetylcholine receptors by strychnine

Functional uncoupling of inhibitory interneurons plays an important role in short-term sensitization of Aplysia gill and siphon withdrawal reflex

Ligand‐gated ion channels opened by 5‐HT in molluscan neurones

Contact Info

Product

Resources

About