Low- and high-voltage-activated calcium currents in rat spinal dorsal horn neurons

1990 ◽  
Vol 63 (2) ◽  
pp. 273-285 ◽  
Author(s):  
P. D. Ryu ◽  
M. Randic

1. Calcium currents in immature rat spinal dorsal horn neurons in transverse slices were studied with the single-electrode voltage-clamp technique. Using experimental conditions that minimized voltage-dependent Na+ and K+ currents, we distinguished low- and high-voltage-activated calcium currents on the basis of their voltage dependence and sensitivity to the Ca2(+)-channel agonist and antagonist drugs. 2. The low-voltage-activated transient calcium current is evoked with weak depolarizing voltage commands. It begins to activate at potentials positive to -70 mV and increases in amplitude and rate of decay with depolarization, the peak values being reached between -40 and -30 mV. The current is fully activated at a holding potential of about -110 mV. Steady-state inactivation is complete at potentials in the range of -60 to -50 mV. 3. The transient component of the high-threshold calcium current appears at membrane potentials close to -40 mV and slowly decays within several hundreds of milliseconds. The amplitude of the current increases with more negative holding potentials (-100 to -40 mV). 4. The sustained component of the high-threshold calcium current seems to activate at potentials positive to -40 mV and exhibits little inactivation during 0.3- to 0.5-s depolarizing commands. This component is better isolated at more depolarized holding potentials (between -40 and -30 mV) that inactivate the transient components of the low- and high-threshold calcium currents. 5. A rundown of calcium currents was seen in dorsal horn cells. The time stability of the transient and sustained components of the high-threshold calcium current was lower than that of the low-threshold transient current. The latter current seemed to be insensitive up to 1 h. 6. (-)-Bay K 8644 (1-10 microM), a dihydropyridine agonist, enhanced the high-threshold calcium current, in particular the sustained component, but not the transient low-threshold calcium current. The dihydropyridine antagonist nifedipine (5-50 microM) selectively reduced the sustained component of the high-threshold calcium current while having little or no effect on the transient components of the low- and high-threshold calcium currents. 7. Cadmium ions (60-100 microM) and cobalt ions (2 mM) markedly reduced both components of the high-threshold calcium current, and Cd2+ only slightly decreased the low-threshold transient current. However, all three components are indiscriminately blocked by higher concentrations of Cd2+ and Co2+.(ABSTRACT TRUNCATED AT 400 WORDS)

2005 ◽  
Vol 102 (1) ◽  
pp. 152-164 ◽  
Author(s):  
Jungang Wang ◽  
Mikito Kawamata ◽  
Akiyoshi Namiki

Background To gain a better understanding of spinal cord injury (SCI)-induced central neuropathic pain, the authors investigated changes in properties of spinal dorsal horn neurons located rostrally and caudally to the lesion and their sensitivity to morphine in rats after SCI. Methods The right spinal cord of Sprague-Dawley rats was hemisected at the level of L2. At 10 to 14 days after the SCI, when mechanical hyperalgesia/allodynia had fully developed, spontaneous activity and evoked responses to mechanical stimuli of wide-dynamic-range (WDR) and high-threshold neurons rostral and caudal to the lesion were recorded. Effects of cumulative doses of systemic (0.1-3 mg/kg) and spinal (0.1-5 microg) administration of morphine on spontaneous activity and evoked responses to the stimuli of the neurons were evaluated. Results Spontaneous activity significantly increased in WDR neurons both rostral and caudal to the SCI site, but high-frequency background discharges with burst patterns were only observed in neurons rostral to the SCI site. Significant increases in responses to the mechanical stimuli were seen both in WDR and high-threshold neurons located both rostrally and caudally to the lesion. The responses to nonnoxious and noxious stimuli were significantly greater in caudal WDR neurons than in rostral WDR neurons. In contrast, the responses to pinch stimuli were significantly higher in rostral high-threshold neurons than those in caudal high-threshold neurons. Systemically administered morphine had a greater effect on responses to nonnoxious and noxious stimuli of rostral WDR neurons than those of caudal WDR neurons. Spinally administered morphine significantly suppressed responses of WDR neurons in SCI animals to nonnoxious stimuli compared with those in sham-operated control animals. Conclusions The findings suggest that changes in properties of spinal dorsal horn neurons after SCI are caused by different mechanisms, depending on the classification of the neurons and their segmental locations.


1997 ◽  
Vol 77 (5) ◽  
pp. 2499-2514 ◽  
Author(s):  
E. Carstens

Carstens, E. Responses of rat spinal dorsal horn neurons to intracutaneous microinjection of histamine, capsaicin, and other irritants. J. Neurophysiol. 77: 2499–2514, 1997. To investigate the spinal processing of cutaneous pruritic and algesic stimuli, single-unit recordings were made from wide-dynamic-range-type lumbar spinal dorsal horn neurons in pentobarbital-sodium-anesthetized rats. Neuronal responses were recorded to mechanical and noxious thermal stimuli, as well as to microinjection (1 μl) of histamine (0.01–10% = 9 × 10−1–9 × 10−4 M), capsaicin (0.1% = 3.3 × 10−3 M), or other algesic chemicals into skin within the receptive field via intracutaneously placed needles. Most (84%) of the 89 neurons responded to intracutaneous (ic) microinjection of histamine with a brief phasic discharge followed by an afterdischarge of variable (s to min) duration. Ten minutes after ic microinjection of histamine (but not NaCl), there was a significant increase in the mean area of the low-threshold (but not high-threshold) portion of unit mechanical receptive fields. However, responses to graded pressure stimuli were not significantly affected after histamine. Responses did not exhibit significant tachyphylaxis when histamine microinjections were repeated at 5- or 10-min intervals. Unit responses significantly increased in a dose-related manner to microinjection of histamine at concentrations ranging across 4 orders of magnitude. Within 30 s after ic microinjection of the H1 antagonist cetirizine, unit responses to ic histamine delivered at the same skin site were significantly attenuated. Unit responses to histamine, as well as to noxious thermal stimulation, were significantly reduced after systemic administration of morphine (3.5 mg/kg ip) in a naloxone-reversible manner. Application of a mechanical rub, scratch, or a noxious heat stimulus during the unit's ongoing response to ic histamine produced a brief and marked excitation, often followed by a period of reduced ongoing discharge. Unit responses to histamine were markedly suppressed by electrical stimulation in the midbrain periaqueductal gray. Most (79%) histamine-responsive units tested also responded to ic microinjection of capsaicin. After the initial microinjection of capsaicin, subsequent responses to histamine and capsaicin microinjections were significantly reduced. Units also responded to ic ethanol (capsaicin vehicle) in a dose-related manner, and showed tachyphylaxis to repeated ic ethanol at 80% but not at 8%. The mean response to 80% ethanol was significantly smaller than to 0.1% capsaicin. All units tested also responded to topical application of mustard oil (50%) and ic serotonin (30 μg). The results are discussed in terms of theories that attempt to reconcile psychophysical and clinical observations of pain and itch sensation.


1995 ◽  
Vol 83 (6) ◽  
pp. 1312-1320 ◽  
Author(s):  
Hiroshi Uchida ◽  
Kazuhiro Kishikawa ◽  
J. G. Collins

Abstract Background Pentobarbital reduces low-threshold receptive field (RF) size and enhances responses of some spinal dorsal horn neurons to noxious stimulation in cats. To better understand the effects of general anesthetics on spinal sensory processing, this study was designed to determine if intravenous propofol and ketamine have similar effects.


2009 ◽  
Vol 13 (S1) ◽  
Author(s):  
M. Gassner ◽  
M. Wagner ◽  
H. Fischer ◽  
R. Drdla ◽  
T. Jäger ◽  
...  

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