Effects of Calcium Channel Antagonist Flunarizine on Parvalbumin- and Calbindin-immunoreactive Structures in Experimental Spinal Cord Ischemia

✓ The potent, centrally active, calcium channel antagonist, nimodipine, was utilized in a highly predictive “spinal stroke” model in order to investigate the potential pathophysiological effects of calcium flux in spinal injury, as well as to evaluate the potential therapeutic role of the newly developed dihydropyridine derivatives in ischemic central nervous system injury. Nimodipine, administered before or after ischemia, at doses shown to be effective in improving cerebral blood flow and in dilating central blood vessels, failed to improve either the histopathological changes or the functional deficit caused by temporary aortic occlusion in the unanesthetized rabbit.

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ω-Agatoxin IVA, a P-Type Calcium Channel Antagonist, Reduces Nociceptive Processing in Spinal Cord Neurons with Input From the Inflamed But Not From the Normal Knee Joint - An Electrophysiological Study in the RatIn Vivo

European Journal of Neuroscience ◽

10.1111/j.1460-9568.1997.tb01386.x ◽

1997 ◽

Vol 9 (10) ◽

pp. 2193-2201 ◽

Cited By ~ 48

Author(s):

J. Nebe ◽

H. Vanegas ◽

V. Neugebauer ◽

H.-G. Schaible

Keyword(s):

Spinal Cord ◽

Knee Joint ◽

Calcium Channel ◽

Calcium Channel Antagonist ◽

Electrophysiological Study ◽

Spinal Cord Neurons ◽

Normal Knee ◽

Nociceptive Processing ◽

P Type

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Comparative Effects of theN-Methyl-d-aspartate Antagonist MK-801 and the Calcium Channel Blocker KB-2796 on Neurologic and Metabolic Recovery after Spinal Cord Ischemia

Experimental Neurology ◽

10.1006/exnr.1997.6680 ◽

1998 ◽

Vol 149 (1) ◽

pp. 203-208 ◽

Cited By ~ 19

Author(s):

Viera Danielisová ◽

Mikuláš Chavko

Keyword(s):

Spinal Cord ◽

Calcium Channel ◽

Calcium Channel Blocker ◽

Channel Blocker ◽

Spinal Cord Ischemia ◽

Mk 801 ◽

Metabolic Recovery

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Calcium Channel Subtypes in Lamprey Sensory and Motor Neurons

Journal of Neurophysiology ◽

10.1152/jn.1997.78.3.1334 ◽

1997 ◽

Vol 78 (3) ◽

pp. 1334-1340 ◽

Cited By ~ 52

Author(s):

A. El Manira ◽

N. Bussières

Keyword(s):

Spinal Cord ◽

Calcium Channels ◽

Calcium Channel ◽

Sensory Neurons ◽

Motor Neurons ◽

Calcium Channel Antagonist ◽

Calcium Currents ◽

Spinal Cord Neurons ◽

Channel Current ◽

Dorsal Cells

El Manira, A. and N. Bussières. Calcium channel subtypes in lamprey sensory and motor neurons. J. Neurophysiol. 78: 1334–1340, 1997. Pharmacologically distinct calcium channels have been characterized in dissociated cutaneous sensory neurons and motoneurons of the larval lamprey spinal cord. To enable cell identification, sensory dorsal cells and motoneurons were selectively labeled with fluorescein-coupled dextran amine in the intact spinal cord in vitro before dissociation. Calcium channels present in sensory dorsal cells, motoneurons, and other spinal cord neurons were characterized with the use of whole cell voltage-clamp recordings and specific calcium channel agonist and antagonists. The results show that a transient low-voltage-activated (LVA) calcium current was present in a proportion of sensory dorsal cells but not in motoneurons, whereas high-voltage-activated (HVA) calcium currents were seen in all neurons recorded. The different components of HVA current were dissected pharmacologically and similar results were obtained for both dorsal cells and motoneurons. The N-type calcium channel antagonist ω-conotoxin-GVIA(ω-CgTx) blocked >70% of the HVA current. A large part of the ω-CgTx block was reversed after washout of the toxin. The L-type calcium channel antagonist nimodipine blocked ∼15% of the total HVA current. The dihydropyridine agonist (±)-BayK 8644 markedly increased the amplitude of the calcium channel current. The BayK-potentiated current was not affected by ω-CgTx, indicating that the reversibility of the ω-CgTx effect is not due to a blockade of L-type channels. Simultaneous application of ω-CgTx and nimodipine left ∼15% of the HVA calcium channel current, a small part of which was blocked by the P/Q-type channel antagonist ω-agatoxin-IVA. In the presence of the three antagonists, the persistent residual current (∼10%) was completely blocked by cadmium. Our results provide evidence for the existence of HVA calcium channels of the N, L, and P/Q types and other HVA calcium channels in lamprey sensory neurons and motoneurons. In addition, certain types of neurons express LVA calcium channels.

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Effects of ω-Agatoxin IVA, a P-Type Calcium Channel Antagonist, on the Development of Spinal Neuronal Hyperexcitability Caused by Knee Inflammation in Rats

Journal of Neurophysiology ◽

10.1152/jn.1999.81.6.2620 ◽

1999 ◽

Vol 81 (6) ◽

pp. 2620-2626 ◽

Cited By ~ 17

Author(s):

Johannes Nebe ◽

Andrea Ebersberger ◽

Horacio Vanegas ◽

Hans-Georg Schaible

Keyword(s):

Spinal Cord ◽

Knee Joint ◽

Calcium Channels ◽

Calcium Channel ◽

Calcium Channel Antagonist ◽

Dynamic Range ◽

Control Group ◽

Spinal Cord Neurons ◽

Neuronal Hyperexcitability ◽

P Type

Effects of ω-agatoxin IVA, a P-type calcium channel antagonist, on the development of spinal neuronal hyperexcitability caused by knee inflammation in rats. Both N- and P-type high-threshold calcium channels are located presynaptically in the CNS and are involved in the release of transmitters. To investigate the importance of P-type calcium channels in the generation of inflammation-evoked hyperexcitability of spinal cord neurons, electrophysiological recordings were made from wide-dynamic-range neurons with input from the knee joint in the anesthetized rat. The responses of each neuron to innocuous and noxious pressure onto the knee and the ankle were continuously assessed before and during the development of an inflammation in the knee joint induced by the injections of K/C into the joint cavity. The specific antagonist at P-type calcium channels ω-agatoxin was administered into a 30-μl trough on the spinal cord surface above the recorded neuron. In most neurons the application of ω-agatoxin before induction of inflammation slightly enhanced the responses to pressure onto the knee and ankle or left them unchanged. Two different protocols were then followed. In the control group (13 rats) only Tyrode was administered to the spinal cord during and after induction of inflammation. In these neurons the responses to mechanical stimuli applied to both the inflamed knee and to the noninflamed ankle showed a significant increase over 4 h. In the experimental group (12 rats) ω-agatoxin was applied during knee injection and in five 15-min periods up to 180 min after kaolin. This prevented the increase of the neuronal responses to innocuous pressure onto the knee and to innocuous and noxious pressure onto the ankle; only the responses to noxious pressure onto the knee were significantly enhanced during development of inflammation. Thus the development of inflammation-evoked hyperexcitability was attenuated by ω-agatoxin, and this suggests that P-type calcium channels in the spinal cord are involved in the generation of inflammation-evoked hyperexcitability of spinal cord neurons. Finally, when ω-agatoxin was administered to the spinal cord 4 h after the kaolin injection, i.e., when inflammation-evoked hyperexcitability was fully established, the responses to innocuous and noxious pressure onto the knee were reduced by 20–30% on average. The shift in the effect of ω-agatoxin, from slight facilitation or no change of the responses before inflammation to inhibition in the state of hyperexcitability, indicates that P-type calcium channels are important for excitatory synaptic transmission involved in the maintenance of inflammation-evoked hyperexcitability.

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