The Experts below are selected from a list of 252 Experts worldwide ranked by ideXlab platform
S C Oneill - One of the best experts on this subject based on the ideXlab platform.
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the effect of Tetracaine on stimulated contractions sarcoplasmic reticulum ca2 content and membrane current in isolated rat ventricular myocytes
The Journal of Physiology, 1998Co-Authors: C L Overend, S C Oneill, D A EisnerAbstract:1The effects of Tetracaine were examined on rat ventricular myocytes. In both field-stimulated and voltage-clamped cells Tetracaine (100–200 μM) produced an initial decrease of contraction before a recovery towards the control level. Removal of Tetracaine produced a transient overshoot of contraction to levels greater than the control. 2The transient decrease of contraction produced by Tetracaine was accompanied by a small transient increase in the integral of the L-type Ca2+ current and a larger transient decrease of the Na+-Ca2+ exchange current on repolarization. These are attributed to decreased systolic release of Ca2+. On removal of Tetracaine there was an increase of the Na+-Ca2+ exchange current. Before the addition of Tetracaine, calculated Ca2+ influx and efflux across the sarcolemma were approximately equal. On adding Tetracaine, efflux was transiently less than influx and, on removal of Tetracaine, efflux was greater than influx. 3These changes in Ca2+ fluxes result in an increase of cell Ca2+ during exposure to Tetracaine. The calculated magnitude of this increase was equal to that measured directly by applying caffeine (20 mM) to release sarcoplasmic reticulum (SR) Ca2+ and integrating the resulting Na+-Ca2+ exchange current. 4It is concluded that the effects of Tetracaine can be accounted for by depression of calcium-induced Ca2+ release (CICR). The response is transient because the inhibition is compensated for by an increase of SR Ca2+ content such that there is no steady-state effect on the magnitude of the systolic Ca2+ transient. The consequences of this result for the effects of other modulators of CICR are discussed.
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the effect of Tetracaine on supontaneous ca2 release and sarcoplasmic reticulum calcium content in rat ventricular myocytes
The Journal of Physiology, 1997Co-Authors: C L Overend, D A Eisner, S C OneillAbstract:1. The effects of Tetracaine were studied on voltage-clamped rat ventricular myocytes, which exhibited Ca2+ overload as identified by spontaneous Ca2+ release from the sarcoplasmic reticulum (SR) as shown by the associated contractions. This Ca2+ release was initially abolished by Tetracaine before returning at a lower frequency, but greater amplitude, than the control. On removal of Tetracaine, there was a burst of spontaneous Ca2+ release activity. All these effects were dose dependent, from 25 to 200 microM Tetracaine. 2. The spontaneous Ca2+ release activated an inward Na(+)-Ca2+ exchange current as Ca2+ was pumped out of the cell. The integral of this current (i.e. the Ca2+ efflux) was increased in the presence of Tetracaine. The calcium efflux per unit time was unaffected by Tetracaine. 3. The SR Ca2+ content was increased by Tetracaine, as shown by the integral of the caffeine-evoked Na(+)-Ca2+ exchange current. The increase of SR Ca2+ content was equal to the extra Ca2+ lost from the cell during the burst on removal of Tetracaine, and to estimates of the extra calcium gained over the quiescent period following addition of Tetracaine. 4. It is concluded that partial inhibition of calcium-induced calcium release increases SR Ca2+ content. In the steady state, cell Ca2+ balance is maintained as the lower frequency of spontaneous release (that activates efflux) is compensated for by their greater size.
Jonathan B Cohen - One of the best experts on this subject based on the ideXlab platform.
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interactions between 3 trifluoromethyl 3 m 125i iodophenyl diazirine and Tetracaine phencyclidine or histrionicotoxin in thetorpedo species nicotinic acetylcholine receptor ion channel
Molecular Pharmacology, 2001Co-Authors: Martin J Gallagher, David C Chiara, Jonathan B CohenAbstract:: 3-(Trifluoromethyl)-3-(m-[(125)I]iodophenyl)diazirine ([(125)I]TID) and [(3)H]Tetracaine, an aromatic amine, are noncompetitive antagonists (NCAs) of the Torpedo species nicotinic acetylcholine receptor (nAChR), which have been shown by photoaffinity labeling to bind to a common site in the ion channel in the closed state. Although Tetracaine and TID bind to the same site, the amine NCAs phencyclidine (PCP) and histrionicotoxin (HTX), which are also believed to bind within the ion channel, interact competitively with Tetracaine but allosterically with TID. To better characterize drug interactions within the nAChR ion channel in the closed state, we identified the amino acids photoaffinity labeled by [(125)I]TID in the presence of Tetracaine, PCP, or HTX. In the absence of other drugs, [(125)I]TID reacts with alphaLeu-251 (alphaM2-9) and alphaVal-255 (alphaM2-13) and the homologous residues in each of the other subunits. None of the NCAs shifted the sites of [(125)I]TID labeling to other residues within the ion channel. Tetracaine inhibited [(125)I]TID labeling of M2-9 and M2-13 without changing the relative(125)I incorporation at these positions, whereas PCP and HTX each altered the pattern of [(125)I]TID incorporation at M2-9 and M2-13. These results indicate that Tetracaine and TID bind in a mutually exclusive manner to a common site in the closed channel that is spatially separated from the binding sites for PCP and HTX.
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identification of amino acids of the torpedo nicotinic acetylcholine receptor contributing to the binding site for the noncompetitive antagonist 3 h Tetracaine
Molecular Pharmacology, 1999Co-Authors: Martin J Gallagher, Jonathan B CohenAbstract:: [(3)H]Tetracaine is a noncompetitive antagonist of the Torpedo nicotinic acetylcholine receptor (nAChR) that binds with high affinity in the absence of cholinergic agonist (K(eq) = 0.5 microM) and weakly (K(eq) = 30 microM) in the presence of agonist (i.e., to nAChR in the desensitized state). In the absence of agonist, irradiation at 302 nm of nAChR-rich membranes equilibrated with [(3)H]Tetracaine results in specific photoincorporation of [(3)H]Tetracaine into each nAChR subunit. In this report, we identify the amino acids of each nAChR subunit specifically photolabeled by [(3)H]Tetracaine that contribute to the high-affinity binding site. Subunits isolated from nAChR-rich membranes photolabeled with [(3)H]Tetracaine were subjected to enzymatic digestion, and peptides containing (3)H were purified by SDS-polyacrylamide gel electrophoresis followed by reversed phase HPLC. N-terminal sequence analysis of the isolated peptides demonstrated that [(3)H]Tetracaine specifically labeled two sets of homologous hydrophobic residues (alphaLeu(251), betaLeu(257), gammaLeu(260), and deltaLeu(265); alphaVal(255) and deltaVal(269)) as well as alphaIle(247) and deltaAla(268) within the M2 hydrophobic segments of each subunit. The labeling of these residues establishes that the high-affinity [(3)H]Tetracaine-binding site is located within the lumen of the closed ion channel and provides a definition of the surface of the M2 helices facing the channel lumen.
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photoaffinity labeling the torpedo nicotinic acetylcholine receptor with 3h Tetracaine a nondesensitizing noncompetitive antagonist
Molecular Pharmacology, 1999Co-Authors: Richard E Middleton, Nina P Strnad, Jonathan B CohenAbstract:Tetracaine ( N , N -dimethylaminoethyl-4-butylaminobenzoate) and related N , N -dialkylaminoethyl substituted benzoic acid esters have been used to characterize the high-affinity binding site for aromatic amine noncompetitive antagonists in the Torpedo nicotinic acetylcholine receptor (nAChR). [3H]Tetracaine binds at equilibrium to a single site with a K eq value of 0.5 μM in the absence of agonist or presence of α-bungarotoxin and with a K eq value of 30 μM in the presence of agonist (i.e., for nAChR in the desensitized state). Preferential binding to nAChR in the absence of agonist is also seen for N , N -DEAE and N , N -diethylaminopropyl esters, both binding with 10-fold higher affinity in the absence of agonist than in the presence, and for the 4-ethoxybenzoic acid ester of N , N -diethylaminoethanol, but not for the 4-amino benzoate ester (procaine). Irradiation at 302 nm of nAChR-rich membranes equilibrated with [3H]Tetracaine resulted in covalent incorporation with similar efficiency into nAChR α, β, γ, and δ subunits. The pharmacological specificity of nAChR subunit photolabeling as well as its dependence on [3H]Tetracaine concentration establish that the observed photolabeling is at the high-affinity [3H]Tetracaine-binding site. Within α subunit, ≥95% of specific photolabeling was contained within a 20-kilodalton proteolytic fragment beginning at Ser173 that contains the M1 to M3 hydrophobic segments. With all four subunits contributing to [3H]Tetracaine site, the site in the closed channel state of the nAChR is most likely within the central ion channel domain.
D A Eisner - One of the best experts on this subject based on the ideXlab platform.
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the effect of Tetracaine on stimulated contractions sarcoplasmic reticulum ca2 content and membrane current in isolated rat ventricular myocytes
The Journal of Physiology, 1998Co-Authors: C L Overend, S C Oneill, D A EisnerAbstract:1The effects of Tetracaine were examined on rat ventricular myocytes. In both field-stimulated and voltage-clamped cells Tetracaine (100–200 μM) produced an initial decrease of contraction before a recovery towards the control level. Removal of Tetracaine produced a transient overshoot of contraction to levels greater than the control. 2The transient decrease of contraction produced by Tetracaine was accompanied by a small transient increase in the integral of the L-type Ca2+ current and a larger transient decrease of the Na+-Ca2+ exchange current on repolarization. These are attributed to decreased systolic release of Ca2+. On removal of Tetracaine there was an increase of the Na+-Ca2+ exchange current. Before the addition of Tetracaine, calculated Ca2+ influx and efflux across the sarcolemma were approximately equal. On adding Tetracaine, efflux was transiently less than influx and, on removal of Tetracaine, efflux was greater than influx. 3These changes in Ca2+ fluxes result in an increase of cell Ca2+ during exposure to Tetracaine. The calculated magnitude of this increase was equal to that measured directly by applying caffeine (20 mM) to release sarcoplasmic reticulum (SR) Ca2+ and integrating the resulting Na+-Ca2+ exchange current. 4It is concluded that the effects of Tetracaine can be accounted for by depression of calcium-induced Ca2+ release (CICR). The response is transient because the inhibition is compensated for by an increase of SR Ca2+ content such that there is no steady-state effect on the magnitude of the systolic Ca2+ transient. The consequences of this result for the effects of other modulators of CICR are discussed.
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the effect of Tetracaine on supontaneous ca2 release and sarcoplasmic reticulum calcium content in rat ventricular myocytes
The Journal of Physiology, 1997Co-Authors: C L Overend, D A Eisner, S C OneillAbstract:1. The effects of Tetracaine were studied on voltage-clamped rat ventricular myocytes, which exhibited Ca2+ overload as identified by spontaneous Ca2+ release from the sarcoplasmic reticulum (SR) as shown by the associated contractions. This Ca2+ release was initially abolished by Tetracaine before returning at a lower frequency, but greater amplitude, than the control. On removal of Tetracaine, there was a burst of spontaneous Ca2+ release activity. All these effects were dose dependent, from 25 to 200 microM Tetracaine. 2. The spontaneous Ca2+ release activated an inward Na(+)-Ca2+ exchange current as Ca2+ was pumped out of the cell. The integral of this current (i.e. the Ca2+ efflux) was increased in the presence of Tetracaine. The calcium efflux per unit time was unaffected by Tetracaine. 3. The SR Ca2+ content was increased by Tetracaine, as shown by the integral of the caffeine-evoked Na(+)-Ca2+ exchange current. The increase of SR Ca2+ content was equal to the extra Ca2+ lost from the cell during the burst on removal of Tetracaine, and to estimates of the extra calcium gained over the quiescent period following addition of Tetracaine. 4. It is concluded that partial inhibition of calcium-induced calcium release increases SR Ca2+ content. In the steady state, cell Ca2+ balance is maintained as the lower frequency of spontaneous release (that activates efflux) is compensated for by their greater size.
C L Overend - One of the best experts on this subject based on the ideXlab platform.
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the effect of Tetracaine on stimulated contractions sarcoplasmic reticulum ca2 content and membrane current in isolated rat ventricular myocytes
The Journal of Physiology, 1998Co-Authors: C L Overend, S C Oneill, D A EisnerAbstract:1The effects of Tetracaine were examined on rat ventricular myocytes. In both field-stimulated and voltage-clamped cells Tetracaine (100–200 μM) produced an initial decrease of contraction before a recovery towards the control level. Removal of Tetracaine produced a transient overshoot of contraction to levels greater than the control. 2The transient decrease of contraction produced by Tetracaine was accompanied by a small transient increase in the integral of the L-type Ca2+ current and a larger transient decrease of the Na+-Ca2+ exchange current on repolarization. These are attributed to decreased systolic release of Ca2+. On removal of Tetracaine there was an increase of the Na+-Ca2+ exchange current. Before the addition of Tetracaine, calculated Ca2+ influx and efflux across the sarcolemma were approximately equal. On adding Tetracaine, efflux was transiently less than influx and, on removal of Tetracaine, efflux was greater than influx. 3These changes in Ca2+ fluxes result in an increase of cell Ca2+ during exposure to Tetracaine. The calculated magnitude of this increase was equal to that measured directly by applying caffeine (20 mM) to release sarcoplasmic reticulum (SR) Ca2+ and integrating the resulting Na+-Ca2+ exchange current. 4It is concluded that the effects of Tetracaine can be accounted for by depression of calcium-induced Ca2+ release (CICR). The response is transient because the inhibition is compensated for by an increase of SR Ca2+ content such that there is no steady-state effect on the magnitude of the systolic Ca2+ transient. The consequences of this result for the effects of other modulators of CICR are discussed.
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the effect of Tetracaine on supontaneous ca2 release and sarcoplasmic reticulum calcium content in rat ventricular myocytes
The Journal of Physiology, 1997Co-Authors: C L Overend, D A Eisner, S C OneillAbstract:1. The effects of Tetracaine were studied on voltage-clamped rat ventricular myocytes, which exhibited Ca2+ overload as identified by spontaneous Ca2+ release from the sarcoplasmic reticulum (SR) as shown by the associated contractions. This Ca2+ release was initially abolished by Tetracaine before returning at a lower frequency, but greater amplitude, than the control. On removal of Tetracaine, there was a burst of spontaneous Ca2+ release activity. All these effects were dose dependent, from 25 to 200 microM Tetracaine. 2. The spontaneous Ca2+ release activated an inward Na(+)-Ca2+ exchange current as Ca2+ was pumped out of the cell. The integral of this current (i.e. the Ca2+ efflux) was increased in the presence of Tetracaine. The calcium efflux per unit time was unaffected by Tetracaine. 3. The SR Ca2+ content was increased by Tetracaine, as shown by the integral of the caffeine-evoked Na(+)-Ca2+ exchange current. The increase of SR Ca2+ content was equal to the extra Ca2+ lost from the cell during the burst on removal of Tetracaine, and to estimates of the extra calcium gained over the quiescent period following addition of Tetracaine. 4. It is concluded that partial inhibition of calcium-induced calcium release increases SR Ca2+ content. In the steady state, cell Ca2+ balance is maintained as the lower frequency of spontaneous release (that activates efflux) is compensated for by their greater size.
David Moher - One of the best experts on this subject based on the ideXlab platform.
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how effective is Tetracaine 4 gel before a venipuncture in reducing procedural pain in infants a randomized double blind placebo controlled trial
BMC Pediatrics, 2007Co-Authors: Brigitte Lemyre, Debora L Hogan, Isabelle Gaboury, Rebecca Sherlock, Colline Blanchard, David MoherAbstract:Procedural pain relief is sub-optimal in neonates. Topical Tetracaine provides pain relief in children. Evidence of its efficacy and safety in neonates is limited. The objective of this study was to assess the efficacy and safety of topical Tetracaine on the pain response of neonates during a venipuncture.
