Sensitization of neonatal rat lumbar motoneuron by the inflammatory pain mediator bradykinin
- Aix-Marseille Université and CNRS, France
- Aix Marseille Université and INSERM, France
- Hungarian Academy of Sciences, Hungary
- Pázmány Péter Catholic University, Hungary
- Cornell University, United States
Figures
Figure 1 with 1 supplement
Bradykinin potentiates the gain of sensory inputs into the motor system.
(A) Drawing of a midsagittally hemisected rat spinal cord illustrating localized Bk application to the lumbar motor column, and dorsal (DR) and ventral (VR) roots used for reflex testing. (B) …
Figure 1—figure supplement 1
At the right, five superimposed responses recorded under spantide (2 µM) from the L5 ventral root of an hemichord preparation and induced by stimulations of the ipsilateral dorsal root before (control, black trace) and after local application of low concentrations of Bk (1 µM pipette concentration, red trace).
At the left, group means quantification of the PSTH for the transient short latency and long-lasting reflexes computed over a window 10–40 ms and 500–4000 ms post stimulus, respectively, before …
Figure 2
Bradykinin enhances repetitive firing and promotes self-sustained spiking.
(A–C) Typical responses of a motoneuron to incrementing 1-s current injections (A) with its respective frequency–current (B) and voltage–current (C) relationships before (black traces) and after …
Figure 3 with 1 supplement
Bradykinin depolarizes lumbar motoneurons by a direct postsynaptic action of B2 receptors.
(A) Voltage trace in response to bradykinin (Bk) collected under kynurenate (1.5 mM). The asterisk indicates the point shown by the trace at right with higher temporal resolution, where spikelets …
Figure 3—figure supplement 1
At the left, superimposed voltage traces recorded from a L5 motoneuron in response to bradykinin (Bk) collected under TTX (0.5 µM) before and after the application of spantide (2 µM).
At the right, histogram plotting the peak amplitude of membrane depolarizations induced by Bk before (black) and after (red) the superfusion of the medium. ns, not significant (Wilcoxon paired test).
Figure 4
Bradykinin inhibits a leak K+ current and activates a Na+-dependent nonselective cationic current.
(A) Representative inward current induced by bradykinin (Bk, 8 µM) in lumbar motoneuron. Voltage clamp, Holding potential, −70 mV. (B) Dose-response curve of Bk-induced changes in peak holding …
Figure 5
Pharmacological profile of the bradykinin-induced current.
(A1–C1) At the left, superimposed I–V relationships reconstructed from voltage ramp data (representative data in inserts) before (black trace) and after (red trace with filled circles) quinidine …
Figure 6
The Bk-induced depolarization of lumbar motoneurons is associated with [Ca2+]i rise in dendrites.
(A) z-projection of two-photon image stack showing cells loaded by bolus injection of OGB1-AM (1 mM) and SR-101 (300 µM). (B) Bradykinin (Bk, 8 µM) increases calcium levels in the motoneuron somata. …
Figure 7
Signal transduction mechanism underlying the Bk effects.
(A–F) At the left, superimposed voltage traces under TTX (0.5 µM) and TEA (10 mM) in response to bradykinin (Bk, 8 µM) before (black) and after (red) GDPßS (2 mM, A), U73122 (10 µM, B), Xestospongin …
Figure 8
Overview of the signal transduction cascade for excitatory actions of Bk on lumbar motoneurons.
InsP3, inositol 1,4,5-trisphosphate; PIP2, phosphatidylinositol-4,5-diphosphate; PLC, Phospholipase C; ER, endoplasmic reticulum.
Tables
Table 1
Effects of bradykinin on passive and active membrane properties of lumbar motoneurons
| Control | Bradykinin | |
|---|---|---|
| N | 10 | 10 |
| Rm (MΩ) | 55.6 ± 5.4* | 62.9 ± 7.2 |
| AP amp (mV) | 67.0 ± 2.3* | 63.7 ± 2.2 |
| AP dur (ms) | 0.51 ± 0.02 | 0.51 ± 0.02 |
| AP threshold (mV) | −50.0 ± 2.1† | −52.8 ± 2.5 |
| f-I slope (Hz/pA) | 0.05 ± 0.004* | 0.06 ± 0.006 |
| Rheobase (pA) | 528 ± 118* | 299 ± 156 |
| sADP (mV) | 11.2 ± 1.4† | 18 ± 2.6 |
| AHP amp (mV) | −9.1 ± 0.9* | −11.2 ± 1.5 |
| AHP dur (ms) | 41.1 ± 2.5* | 48.6 ± 3.4 |
| Sag (%) | 12 ± 2.6 | 12.3 ± 2.5 |
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Statistical significance was assessed by a Wilcoxon paired test.
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*
p < 0.05,
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†
p < 0.01,
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n = number of cells. Mean firing frequency was measured at two times the rheobase.
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AHP = afterhyperpolarization.
