High voltage-activated Ca2+ channel currents in isolectin B4-positive and -negative small dorsal root ganglion neurons of rats

Wu, Zi Zhen; Pan, Hui Lin

doi:10.1016/j.neulet.2004.06.067

Cited by 29 publications

(27 citation statements)

References 31 publications

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“…In accordance with the data of Wu and Pan (2004), we found that L-type and P/Q-type calcium channels do not contribute considerably to the high-threshold voltage-activated calcium current in DRG cells, because neither nitrendipine (10 M; n ϭ 4) nor -agatoxin-IVA (0.1 M; n ϭ 9) blocked the current significantly (5 Ϯ 1 and 4 Ϯ 1% inhibition of calcium current amplitude, respectively), whereas -conotoxin-GVIA, a selective N-type calcium channel blocker (3 M), caused a 28 Ϯ 3% inhibition (n ϭ 4). Silperisone (320 M) inhibited both the -conotoxin-sensitive current component and also most of the drug-resistant (R-type) current (Fig.…”

Section: Isolated Hemisected Spinal Cord In Vitrosupporting

confidence: 89%

Tolperisone-Type Drugs Inhibit Spinal Reflexes via Blockade of Voltage-Gated Sodium and Calcium Channels

Kocsis

Farkas²,

Fodor³

et al. 2005

J Pharmacol Exp Ther

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The spinal reflex depressant mechanism of tolperisone and some of its structural analogs with central muscle relaxant action was investigated. Tolperisone (50 -400 M), eperisone, lanperisone, inaperisone, and silperisone (25-200 M) dose dependently depressed the ventral root potential of isolated hemisected spinal cord of 6-day-old rats. The local anesthetic lidocaine (100 -800 M) produced qualitatively similar depression of spinal functions in the hemicord preparation, whereas its blocking effect on afferent nerve conduction was clearly stronger. In vivo, tolperisone and silperisone as well as lidocaine (10 mg/kg intravenously) depressed ventral root reflexes and excitability of motoneurons. However, in contrast with lidocaine, the muscle relaxant drugs seemed to have a more pronounced action on the synaptic responses than on the excitability of motoneurons. Whole-cell measurements in dorsal root ganglion cells revealed that tolperisone and silperisone depressed voltage-gated sodium channel conductance at concentrations that inhibited spinal reflexes. Results obtained with tolperisone and its analogs in the [3 H]batrachotoxinin A 20-␣-benzoate binding in cortical neurons and in a fluorimetric membrane potential assay in cerebellar neurons further supported the view that blockade of sodium channels may be a major component of the action of tolperisone-type centrally acting muscle relaxant drugs. Furthermore, tolperisone, eperisone, and especially silperisone had a marked effect on voltagegated calcium channels, whereas calcium currents were hardly influenced by lidocaine. These data suggest that tolperisonetype muscle relaxants exert their spinal reflex inhibitory action predominantly via a presynaptic inhibition of the transmitter release from the primary afferent endings via a combined action on voltage-gated sodium and calcium channels.2-Methyl-1-(4-methylphenyl)-3-(1-piperidinyl)-1-propanone hydrochloride (tolperisone) is an old, centrally acting muscle relaxant drug that is mainly used for treating muscle spasticities of neurological origin and painful muscle spasms due to rheumatologic conditions. Besides being an effective antispastic agent (Pratzel et al., 1996;Dulin et al., 1998), tolperisone also has analgesic activity in rodents (Sakaue et al., 2004) and in humans (Svensson et al., 2003). It possesses relatively few side effects in humans (Dulin et al., 1998). Other propiophenone muscle relaxants include 1-(4-ethylphenyl)-2-methyl-3-(1-piperidinyl)-1-propanone hydrochloride (eperisone), which is also a registered drug (Bose, 1999), and (Ϫ)-2-(R)-methyl-3-(1-pyrrolidinyl)-1-[4-(trifluoromethyl)phenyl]-propanone hydrochloride (lanperisone; Sakitama et al., 1997) and 1-(4-ethylphenyl)-2-methyl-3-(1-pyrrolidinyl)-1-propanone hydrochloride (inaperisone; Morikawa et al., 1992), two agents that had been tested in human phase III studies but not introduced into the clinical practice. 1-[(4-Fluorobenzyl)dimethylsilylmethyl]piperidine hydrochloride (silperisone), a sila analog of tolperisone (Farkas et ...

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Section: Isolated Hemisected Spinal Cord In Vitrosupporting

confidence: 89%

Tolperisone-Type Drugs Inhibit Spinal Reflexes via Blockade of Voltage-Gated Sodium and Calcium Channels

Kocsis

Farkas²,

Fodor³

et al. 2005

J Pharmacol Exp Ther

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“…The cell suspension was centrifuged (500 rpm; 5 min) to remove the supernatant and replenished with DMEM. Cells were then plated onto a 35-mm culture dish containing poly-L-lysine (50 g/ml)-precoated coverslips and kept for at least 30 min before electrophysiological recordings (Wu and Pan, 2004). Approximately equal number of IB 4 -positive and IB 4 -negative neurons was studied in one rat.…”

Section: Methodsmentioning

confidence: 99%

“…Seals (1-10 G⍀) between the electrode and cell were established in a modified Tyrode's solution containing 140 mM NaCl, 5.4 mM KCl, 1 mM CaCl 2 , 1 mM MgCl 2 , 10 mM HEPES, and 10 mM glucose (pH 7.4 adjusted with NaOH, osmolarity 320 mOsM). After whole-cell configuration was established, the cell membrane capacitance and series resistance were electronically compensated, as described previously (Wu and Pan, 2004). Leakage and capacitative currents were subtracted on-line using the P/4 subtraction protocol.…”

Section: Methodsmentioning

confidence: 99%

“…Barium currents (I Ba ) flowing through Ca 2ϩ channels (Moises et al, 1994;Wu and Pan, 2004) were recorded using extracellular solution consisting of 140 mM tetraethylammonium, 2 mM MgCl 2 , 3 mM BaCl 2 , 10 mM glucose, and 10 mM HEPES (pH 7.4 adjusted with tetraethylammonium-OH, osmolarity 320 mOsM). The pipette solution contained 120 mM CsCl, 1 mM MgCl 2 , 10 mM HEPES, 10 mM EGTA, 4 mM Mg-ATP, and 0.3 mM Na-GTP (pH 7.2 adjusted with CsOH, osmolarity 300 mOsM).…”

Section: Methodsmentioning

confidence: 99%

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Differential Sensitivity of N- and P/Q-Type Ca²+ Channel Currents to a μ Opioid in Isolectin B -Positive and -Negative Dorsal Root Ganglion Neurons

Chen

Pan

2004

J Pharmacol Exp Ther

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Opioids have a selective effect on nociception with little effect on other sensory modalities. However, the cellular mechanisms for this preferential effect are not fully known. Two broad classes of nociceptors can be distinguished based on their growth factor requirements and binding to isolectin B 4 (IB 4 ). In this study, we determined the difference in the modulation of voltage-gated Ca 2ϩ currents by [D-Ala 2 ,N-Me-Phe 4 ,Gly-ol 5 ]-enkephalin (DAMGO, a specific opioid agonist) between IB 4 -positive and -negative small dorsal root ganglion (DRG) neurons. Whole-cell voltage-clamp recordings were performed in acutely isolated DRG neurons in adult rats. Both 1-10 M DAMGO and 1 to 10 M morphine had a greater effect on high voltage-activated Ca 2ϩ currents in IB 4 -negative than IB 4 -positive cells. However, DAMGO had no significant effect on T-type Ca 2ϩ currents in both groups. The N-type Ca 2ϩ current was the major subtype of Ca 2ϩ currents inhibited by DAMGO in both IB 4 -positive and -negative neurons. Although DAMGO had no effect on L-type and R-type Ca 2ϩ currents in both groups, it produced a larger inhibition on N-type and P/Q-type Ca 2ϩ currents in IB 4 -negative than IB 4 -positive neurons. Furthermore, double labeling revealed that there was a significantly higher opioid receptor immunoreactivity in IB 4 -negative than IB 4 -positive cells. Thus, these data suggest that N-and P/Qtype Ca 2ϩ currents are more sensitive to inhibition by the opioids in IB 4 -negative than IB 4 -positive DRG neurons. The differential sensitivity of voltage-gated Ca 2ϩ channels to the opioids in subsets of DRG neurons may constitute an important analgesic mechanism of opioids.The dorsal root ganglion (DRG) neurons and the associated primary afferent nerves transmit different sensory modalities, including nociception to the spinal dorsal horn. The DRG neurons are a mixed population of cells that differ in size, phenotype, and central projections in the dorsal horn. The slowly conducting A␦-and C-fiber afferents are connected to small DRG neurons and transmit primarily nociceptive information. Opioids have a distinct effect on nociception with little effect on other sensory modalities. However, the cellular mechanisms of this differential effect are not fully known. One of the important analgesic mechanisms of opioids is through inhibition of synaptic transmission by acting on voltage-gated Ca 2ϩ channels present on the central terminals of DRG neurons (Rusin and Moises, 1995;Kohno et al., 1999). It has been demonstrated that opioids inhibit voltage-gated Ca 2ϩ channels in dissociated DRG neurons from 10 to 90% (Schroeder and McCleskey, 1993;Moises et al., 1994). It is likely that the large difference of the opioid effect on Ca 2ϩ channels is due to the heterogeneity of DRG neurons studied. The opioid sensitivity and voltage-gated Ca 2ϩ channels in different classes of DRG neurons remain unclear.A novel approach to the classification of DRG neurons is derived from the requirements of subsets of neurons for specific...

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“…Whole cell voltage clamp recordings were performed in cultured hippocampus neurons (63). Barium currents (I Ba) flowing through Ca 2ϩ channels were recorded using an extracellular solution containing 140 mM TEA-Cl, 2 mM MgCl2, 3 mM BaCl2, 10 mM glucose, 10 mM HEPES (pH 7.4 adjusted with TEA-OH, osmolarity 320), and a pipette solution containing 120 mM CsCl, 1 mM MgCl 2, 10 mM HEPES, 10 mM EGTA, 4 mM Mg-ATP, and 0.3 mM Na-GTP (pH 7.2 adjusted with CsOH, osmolarity 300 mOsm).…”

Section: Methodsmentioning

confidence: 99%

GLP-2 potentiates L-type Ca²⁺ channel activity associated with stimulated glucose uptake in hippocampal neurons

Wang

Guan

2010

American Journal of Physiology-Endocrinology and Metabolism

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High voltage-activated Ca2+ channel currents in isolectin B4-positive and -negative small dorsal root ganglion neurons of rats

Cited by 29 publications

References 31 publications

Tolperisone-Type Drugs Inhibit Spinal Reflexes via Blockade of Voltage-Gated Sodium and Calcium Channels

Tolperisone-Type Drugs Inhibit Spinal Reflexes via Blockade of Voltage-Gated Sodium and Calcium Channels

Differential Sensitivity of N- and P/Q-Type Ca²+ Channel Currents to a μ Opioid in Isolectin B -Positive and -Negative Dorsal Root Ganglion Neurons

GLP-2 potentiates L-type Ca²⁺ channel activity associated with stimulated glucose uptake in hippocampal neurons

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High voltage-activated Ca2+ channel currents in isolectin B4-positive and -negative small dorsal root ganglion neurons of rats

Cited by 29 publications

References 31 publications

Tolperisone-Type Drugs Inhibit Spinal Reflexes via Blockade of Voltage-Gated Sodium and Calcium Channels

Tolperisone-Type Drugs Inhibit Spinal Reflexes via Blockade of Voltage-Gated Sodium and Calcium Channels

Differential Sensitivity of N- and P/Q-Type Ca2+ Channel Currents to a μ Opioid in Isolectin B -Positive and -Negative Dorsal Root Ganglion Neurons

GLP-2 potentiates L-type Ca2+ channel activity associated with stimulated glucose uptake in hippocampal neurons

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Product

Resources

About

Differential Sensitivity of N- and P/Q-Type Ca²+ Channel Currents to a μ Opioid in Isolectin B -Positive and -Negative Dorsal Root Ganglion Neurons

GLP-2 potentiates L-type Ca²⁺ channel activity associated with stimulated glucose uptake in hippocampal neurons