Calcium- and sodium-dependent action potentials of mouse spinal cord and dorsal root ganglion neurons in cell culture.

1. The distribution of IH, IIR, and ILEAK was studied in different diameter rat dorsal root ganglion (DRG) neuron cell bodies (neurons). DRG neurons were studied in three diameter ranges: small (19–27 microns), medium (33–37 microns), and large (44-54 microns). IH was defined as a slowly activating inward current evoked by hyperpolarizing voltage steps from a holding potential (HP) of -60 mV, and blocked by 1 mM Cs2+ but not 1 mM Ba2+. Inward rectifier current (IIR) was defined as a rapidly activating current evoked by hyperpolarizations from HP -60 mV, which rectified inwardly around the reversal potential for potassium (EK), and was completely blocked by 100 microM Ba2+. ILEAK was defined as an outward resting current at HP -60 mV, which did not rectify and was blocked by 100 microM Ba2+ but not by 2 mM Cs+. 2. IH was observed in 23 of 23 large, 11 of 12 medium, and in 9 of 20 small diameter DRG neurons tested. Peak IH normalized to membrane surface area was significantly greater in large than in medium or small diameter DRG neurons expressing IH. All neurons exhibiting IH under voltage clamp conditions had short duration action potentials and exhibited time-dependent rectification under current clamp conditions, properties similar to A-type DRG neurons. The 11 small diameter neurons not expressing IH had long duration action potentials and did not exhibit time-dependent rectification, properties similar to C-type DRG neurons. 3. IIR was detected in 18 of 22 medium diameter neurons tested.(ABSTRACT TRUNCATED AT 250 WORDS)

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Interaction of opioids and membrane potential to modulate Ca2+ channels in rat dorsal root ganglion neurons

Journal of Neurophysiology ◽

10.1152/jn.1995.73.5.1793 ◽

1995 ◽

Vol 73 (5) ◽

pp. 1793-1798 ◽

Cited By ~ 22

Author(s):

M. D. Womack ◽

E. W. McCleskey

Keyword(s):

Dorsal Root Ganglion ◽

Sensory Neurons ◽

Action Potentials ◽

Dorsal Root ◽

Dorsal Root Ganglion Neurons ◽

High Threshold ◽

Partial Recovery ◽

Drg Neurons ◽

Ganglion Neurons ◽

Ca2 Channels

1. Using patch-clamp methods, we show that brief prepulses to very positive voltages increase (facilitate) the amplitude of current through Ca2+ channels during a subsequent test pulse in some, but not all, dorsal root ganglion (DRG) sensory neurons. The amplitude of this facilitated current generally increases when the Ca2+ channels are inhibited by activation of the mu-opioid receptor. 2. The facilitated current is blocked by omega-conotoxin GVIA, activates in the range of high-threshold Ca2+ channels, and inactivates at relatively negative holding voltages. Thus facilitated current passes through N-type Ca2+ channels, the same channels that are inhibited by opioids and control neurotransmitter release in sensory neurons. 3. Although maximal facilitation occurs only at unphysiologically high membrane potentials (above +100 mV), some facilitation is seen after prepulses to voltages reached during action potentials. After return to the holding potential, facilitation persists for hundreds of milliseconds, considerably longer than in other neurons. Brief trains of pulses designed to mimic action potentials caused small facilitation (19% of maximal) in a fraction (8 of 24) of opioid-inhibited neurons. 4. We conclude that 1) prepulses to extremely positive voltages can cause partial recovery of Ca2+ channels inhibited by opioids; and 2) small, but detectable, facilitation is also seen after physiological stimulation in some DRG neurons. Facilitation, largely considered a biophysical epiphenomenon because of the extreme voltages used to induce it, appears to be physiologically relevant during opioid inhibition of Ca2+ channels in DRG neurons.

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Block of Na+ currents and suppression of action potentials in embryonic rat dorsal root ganglion neurons by ranolazine

Neuropharmacology ◽

10.1016/j.neuropharm.2012.01.021 ◽

2012 ◽

Vol 62 (7) ◽

pp. 2251-2260 ◽

Cited By ~ 11

Author(s):

Ryoko Hirakawa ◽

Nesrine El-Bizri ◽

John C. Shryock ◽

Luiz Belardinelli ◽

Sridharan Rajamani

Keyword(s):

Dorsal Root Ganglion ◽

Action Potentials ◽

Dorsal Root ◽

Dorsal Root Ganglion Neurons ◽

Na Currents ◽

Ganglion Neurons

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Systematic Administration of B Vitamins Alleviates Diabetic Pain and Inhibits Associated Expression of P2X3 and TRPV1 in Dorsal Root Ganglion Neurons and Proinflammatory Cytokines in Spinal Cord in Rats

Pain Research and Management ◽

10.1155/2020/3740162 ◽

2020 ◽

Vol 2020 ◽

pp. 1-11

Author(s):

Duan-Duan He ◽

Yu Gao ◽

Shan Wang ◽

Zhong Xie ◽

Xue-Jun Song

Keyword(s):

Spinal Cord ◽

Blood Glucose ◽

Dorsal Root Ganglion ◽

Proinflammatory Cytokines ◽

Dorsal Root ◽

B Vitamins ◽

Dorsal Root Ganglion Neurons ◽

Drg Neurons ◽

B Vitamin ◽

Ganglion Neurons

Background. Treatment of diabetic neuropathic pain (DNP) continues to be a major challenge, and underlying mechanisms of DNP remain elusive. We investigated treatment effects of B vitamins on DPN- and DNP-associated alterations of neurochemical signaling in the nociceptive dorsal root ganglion (DRG) neurons and the spinal cord in rats. Methods. DNP was produced in male, adult, Sprague Dawley rats by single i.p. streptozotocin (STZ). Western blot analysis and immunohistochemistry were used to analyze protein expressions in DRG and ELISA to measure the proinflammatory cytokines in the spinal cord. Behaviorally expressed DNP was determined by measuring the sensitivity of hindpaw skin to mechanical and thermal stimulation. Results. There were 87.5% (77/88) rats which developed high blood glucose within 1-2 weeks following STZ injection. Of which, 70.13% (n = 54/77) animals exhibited DNP manifested as mechanical allodynia and/or thermal hyperalgesia. Intraperitoneal administration of vitamins B1/B6/B12 (100/100/2 mg/kg, one or multiple doses) significantly attenuated DNP without affecting the blood glucose. Expressions of P2X3 and TRPV1 in CGRP-positive and IB4-positive DRG neurons as well as the interleukin-1β, tumor necrosis factor-α, and nerve growth factor in the lumbar spinal cord were greatly increased in DNP rats. Such DNP-associated neurochemical alterations were also greatly suppressed by the B-vitamin treatment. Conclusions. B-vitamin treatment can greatly suppress chronic DNP and DNP-associated increased activities of P2X3 and TRPV1 in DRG and the spinal proinflammatory cytokines, which may contribute to the pathogenesis of DNP. Systematic administration of B vitamins can be a strategy for DNP management in clinic.

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