Ming-Cheng Tsai

Anticardiolipin antisera from lupus patients with seizures reduce a GABA receptor-mediated chloride current in snail neurons

The effects of circulating anticardiolipin (ACL) antisera in lupus patients on the LP5 central neuron of snail were studied. Both GABA and glutamate increased a chloride conductance of the LP5 neuron. The ACL antisera decreased the GABA-elicited responses in a concentration dependent manner while it had no effect on glutamate-elicited responses. The ACL antisera affected neither the resting membrane current, nor the membrane conductivity of neuron. Antisera without the activity of anticardiolipin did not decrease the GABA-elicited responses. The seizure incidence of the patients with higher ACL antisera levels is also higher. It is concluded that ACL antisera inhibited the GABA ionophore receptor complex in a snail central neuron.

Analgesic Effect of Lidocaine Patch 5% in the Treatment of Acute Herpes Zoster: A Double-Blind and Vehicle-Controlled Study

Background and Objectives: Although lidocaine patch 5% has been widely used for postherpetic neuralgia, its analgesic effect on the intense pain associated with acute herpes zoster has not been investigated because of its potential hazard to damaged skin. Methods: Forty‐six patients suffering from moderate to severe pain caused by acute herpes zoster infection (within 4 weeks of onset) were enrolled in a randomized, double‐blind, vehicle‐controlled, parallel study. Lidocaine patch 5% or vehicle patch were applied to the intact portion of the painful skin area without blisters at 12‐hour intervals twice a day for 2 consecutive days. Analgesic efficacy and side effect profiles were assessed before and 48 hours after patch application. Results: We found that both groups of patients experienced significant pain relief during rest and movement. Differences of mean reduction of pain intensity between the two groups were 14.7 (4.7‐24.8, P = 0.005) during rest and 10.4 (1.6‐19.3, P = 0.007) during movement, favoring the lidocaine patch. The lidocaine patch produced a greater percentage change in a patients global impression than the vehicle patch. The incidence and severity of adverse events were low with both treatments. Conclusions: This study demonstrates that lidocaine patch 5%, applied twice a day, could serve as a well tolerated and effective modality to relieve moderate to severe pain associated with acute herpes zoster presumably through its pharmacological action and physical barrier effect on sensitized skin.

BURSTING FIRING OF ACTION POTENTIALS IN CENTRAL SNAIL NEURONS ELICITED BY D-AMPHETAMINE : ROLE OF THE ELECTROGENIC SODIUM PUMP

The effects of d-amphetamine on central neurons were studied electrophysiologically in the identifiable RP4 neuron of the African snail, Achatina fulica Ferussac. d-Amphetamine elicited bursting activity from the central RP4 neuron in a concentration-dependent manner. The bursting activity was not blocked in a high magnesium (30 mM) medium, or after a continuous perfusion of propranolol, prazosin, haloperidol, phenobarbital, hexamethonium, d-tubocurarine, atropine, or calcium-free solution containing EDTA or verapamil. These results suggested that the bursting activity elicited by d-amphetamine was not due to: (1) the synaptic effects of neurotransmitters; or (2) the cholinergic or adrenergic receptors of the excitable membrane. However, the bursting activity elicited by d-amphetamine was blocked in the presence of ouabain or in the medium containing potassium-free, low sodium solutions. d-Amphetamine did not elicit the bursting activity of the LP4 neuron in the same ganglia preparation, and did not alter the GABA-elicited currents of the snail neuron. It is concluded, therefore, that d-amphetamine induced a potassium- and sodium-dependent bursting activity of central neurons. The bursting activity of the central neuron may be associated with the sodium pump of the neuron.

The effect of 3,3-di-pyridyl-methyl-1-phenyl-2-indolinone on the nerve terminal currents of mouse skeletal muscles

The effects of 3,3-dipyridyl-methyl-1-phenyl-2-indolinone (DPMPI), a new cognition enhancer, on perineural waveforms were assessed on triangularis sterni nerve-muscle preparations in the mouse. The perineural waveforms were recorded with extracellular electrodes placed in the perineural sheaths of motor nerves. At 64.5 microM, DPMPI decreased the fast potassium current of the nerve terminal. The sodium current, calcium currents and calcium-dependent potassium current of the nerve terminal were not affected. At a greater concentration (215 microM), DPMPI decreased all of the components of the waveforms associated with sodium, potassium and calcium currents. It is concluded that DPMPI affects potassium, as well as sodium currents in the nerve terminal. The effect may contribute to its pharmacological actions on synaptic transmission.

(±)3,4 -Methylenedioxyamphetamine elicits action potential bursts in a central snail neuron

The effects of (+/-)3,4-methylenedioxyamphetamine (MDA) were studied in an identifiable RP4 neuron of the African snail, Achatina fulica Ferussac, using the two-electrode voltage-clamp method. The RP4 neuron generated spontaneous action potentials. Extracellular or intracellular application of MDA elicited action potential bursts of the central RP4 neuron. The action potential bursts elicited by MDA were not blocked when neurons were immersed in high-Mg2+ solution, Ca2+-free solution, nor after continuous perfusion with atropine, d-tubocurarine, propranolol, prazosin, haloperidol, sulpiride or methiothepin. Notably, the induction of action potential bursts was blocked by pretreatment with protein kinase C (PKC) inhibitors, chelerythrine and Ro 31-8220, but not by protein kinase A (PKA) inhibitors, KT-5720 and H89, nor by the phospholipase C (PLC) inhibitor, U73122. PKC activators, i.e., phorbol 12,13-dibutyrate (PDBu) and 1-oleoyl-2-acety-sn-glycerol (OAG; a membrane-permeant DAG analog), facilitate the induction of action potential bursts elicited by MDA. Voltage-clamp studies revealed that MDA decreased the delayed rectifying K+ current (I(KD)) of the RP4 neuron. Further, although Ro 31-8220 did not affect the I(KD), Ro 31-8220 decreased the inhibitory effect of MDA on the I(KD). These results suggest that the generation of action potential bursts elicited by MDA was not due to (1) the synaptic effects of neurotransmitters, (2) the cholinergic, adrenergic, dopaminergic or serotoninergic receptors of the excitable membrane. Instead, the MDA-elicited action potential bursts are closely related to PKC activity and the inhibitory effects on the I(KD).

Effects of territrem-B on cholinergic responses of snail neuron

Effects of territrem-B (TRB), a mycotoxin isolated from a rice culture of Aspergillus terreus, on the central neuron of the snail Achatina fulica were studied electrophysiologically. Territrem-B potentiated the acetylcholine (ACh) induced current of the neuron, while it had no effect on GABA or L-glutamate elicited currents. TRB and neostigmine increased the peak amplitude of the response elicited by the first perfusion of ACh and depressed the increase in current produced by a second perfusion. TRB and neostigmine showed different dose-dependent effects on ACh responses. The results suggested that TRB is a good tool for studying the physiological role of AChE in central neurons.

The effect of 3,3-dipyridylmethyl-1-phenyl-2-indolinone on the neuromuscular transmission in the rodent skeletal muscles

The effects of a cognition enhancer, 3,3-dipyridylmethyl-1-phenyl-2-indolinone (DPMPI) (21.5-645 microM), on neuromuscular transmission were studied electrophysiologically on diaphragms of mouse and rat and the soleus muscle of rat. The drug DPMPI (21.5-645 microM) increased both direct and indirect twitch tension of mouse diaphragm. It also increased (a) the frequency of miniature endplate potentials and (b) the quantal content of endplate potential. However, DPMPI (64.5 microM) affected neither the amplitude of the directly elicited action potential of soleus muscle in the rat nor the magnitude of the resting membrane potential of mouse diaphragm, although DPMPI (215 microM) decreased the amplitude of the compound action potential of phrenic nerve. Based on these results, it is concluded that DPMPI had several effects on neuromuscular transmission, i.e. it (a) facilitated the transmitter releasing process of the motor nerve terminal, (b) decreased the conduction in the phrenic nerve and (c) increased the directly elicited twitch tension.

Interaction of concanavalin A and wheat germ agglutinin with Helix acetylcholine receptors

The effects of lectins concanavalin A (Con A) and wheat germ agglutinin (WGA), were studied on acetylcholine (ACh) responses of physically isolated internally dialyzed Helix aspersa neurons using the concentration clamp method and on the binding of [3H]alpha-bungarotoxin to the cluster of neurons. Con A and WGA have different simple sugar specificity and produced different actions on ACh-evoked Cl conductance responses, which were antagonized by Con A (5 micrograms/ml) but were not altered by WGA. Con A depressed ACh responses when applied extracellularly while it had no effect on ACh responses of the same neuron when added to the intracellular solution, thus indicating that Con A specific glycoproteins are exposed on the surface of the neuron. The studies of the effect of Con A on the properties of the ACh binding site (receptor) have demonstrated, that (1) the onset of desensitization of ACh responses of the dialyzed neurons, determined from the decay of ACh-current from peak to plateau in the continued presence of agonist and best fitted by a double exponential function, was accelerated by Con A; (2) Con A depressed the maximal ACh induced current in a dose response relationship and altered the Hill coefficients; (3) Con A depressed the binding of [3H]alpha-bungarotoxin to the cluster of neurons. These results indicate that Con A receptors on the surface of the neuronal membrane play a regulatory role in the ACh-receptor system and suggest that binding of lectin molecules to their receptors leads to inhibition of binding of ACh to ACh-receptors and to acceleration of the kinetics of desensitization of ACh receptors. All the effects of Con A, that is, on the peak amplitude, desensitization, dose-response relationship of ACh induced current and binding of [3H]alpha-bungarotoxin, could be recovered by D-mannose, a competitive inhibitor of Con A binding to its receptor.(ABSTRACT TRUNCATED AT 250 WORDS)

Ecstasy and methamphetamine elicit action potential bursts via different mechanisms in a central snail neuron.

This study sought to determine the effects of (+) methamphetamine (METH) and its ring-substituted analog (+/-)3,4-methylenedioxymethamphetamine (MDMA; ecstasy) on electrophysiological behavior and their relationships to second messenger systems in an identifiable RP4 neuron of the African snail, Achatina fulica Ferussac. Extracellular application of MDMA at 1mM and METH at 3mM elicited action potential bursts that were not blocked after immersing the neurons in Ca(2+)-free solution. Notably, MDMA- (1mM) elicited action potential bursts were blocked by pretreatment with the protein kinase C (PKC) inhibitors chelerythrine (20 microM) and Ro 31-8220 (20 microM), but not by the PKA inhibitors KT-5720 (10 microM) and H89 (10 microM). The PKC activator phorbol 12,13-dibutyrate (PDBu; 3 microM), but not the PKA activator forskolin (50 microM), facilitated the induction of bursts elicited by MDMA at a lower concentration (0.3mM). In contrast, METH- (3mM) elicited action potential bursts were blocked by pretreatment with KT-5720 (10 microM) and H89 (10 microM), but not by chelerythrine (20 microM) and Ro 31-8220 (20 microM). Forskolin (50 microM), but not PDBu (3 microM) facilitated the induction of bursts elicited by METH at a lower concentration (1mM). Tetraethylammonium chloride (TEA), a blocker of the delayed rectifying K(+) current (I(KD)), did not elicit bursts at a concentration of 5mM but did facilitate the induction of action potential bursts elicited by both METH and MDMA. Voltage clamp studies revealed that both METH and MDMA decreased the TEA-sensitive I(KD) of the RP4 neuron. Forskolin (50 microM) or dibutyryl cAMP (1mM), a membrane-permeable cAMP analog, alone did not elicit action potential bursts. However, co-administration with forskolin (50 microM) and TEA (5mM) or co-administration with dibutyryl cAMP (1mM) and TEA (50mM) elicited action potential bursts in the presence of the PKC inhibitor chelerythrine (20 microM). Similarly, PDBu (10 microM) or phorbol 12-myristate 13-acetate (PMA; 3 microM) alone did not elicit action potential bursts. However, co-administration with PDBu (10 microM) and TEA (5mM) or co-administration with PMA (3 microM) and TEA (5mM) elicited action potential bursts in the presence of the PKA inhibitor KT-5720 (10 microM). These data suggest that action potential bursts in the RP4 neuron were not due to Ca(2+)-dependent synaptic effects. Rather, action potential bursts may be elicited through (1) combined activation of the cAMP-PKA signaling pathway and inhibition of the I(KD) and (2) combined activation of PKC and inhibition of the I(KD).

Neuromuscular blockade of the fetus with pancuronium or pipecuronium for intra‐uterine procedures

Fetal movement during intra‐uterine fetal therapy makes these procedures technically more dificult and increases the likelihood of trauma to the fetus. Pancuronium or pipecuronium were used in a randomised study to temporarily arrest movement in 16 fetuses undergoing intra‐uterine procedures. Under ultrasound guidance, pancuronium or pipecuronium 0.2 mg.kg−1 was injected into the fetal gluteal region. Fetal movements ceased within 4.6 ± 2.3 min in the pancuronium group and 4.5 ± 2.8 min in the pipecuronium group and returned by 115±26 min in the pancuronium group and 121 ± 3 2 min in the pipecuronium group. No adverse effects of the relaxant were observed in the mothers. There bvas no evidence of soft tissue, nerve or muscle damage at the fetal injection site after delivery. Both muscle relaxants provided a safer method for diagnostic and therapeutic procedures. However, four cases in the pancuronium group (50%) developed a fetal tachycardia, and two cases in the same group showed loss of beat‐to‐beat variability. Pipecuronium appeared to be more suitable for intra‐uterine procedures.