scholarly journals Physiological involvement of presynaptic L‐type voltage‐dependent calcium channels in GABA release of cerebellar molecular layer interneurons

2020 ◽  
Vol 155 (4) ◽  
pp. 390-402
Author(s):  
Stéphanie Rey ◽  
Gilliane Maton ◽  
Shin’Ichiro Satake ◽  
Isabel Llano ◽  
Soosung Kang ◽  
...  
Keyword(s):  
Calcium Channels ◽  
Molecular Layer ◽  
Gaba Release ◽  
Voltage Dependent ◽  
Voltage Dependent Calcium Channels ◽  
Cerebellar Molecular Layer

N-Type Voltage-Dependent Calcium Channels Mediate the Nicotinic Enhancement of GABA Release in Chick Brain

1999 ◽  
Vol 81 (2) ◽  
pp. 447-454 ◽  
Author(s):  
Trevor L. Tredway ◽  
Jian-Zhong Guo ◽  
Vincent A. Chiappinelli
Keyword(s):  
Calcium Channels ◽  
Channel Blocker ◽  
Brain Slices ◽  
Gaba Release ◽  
Channel Blockers ◽  
Chick Brain ◽  
Voltage Dependent ◽  
Voltage Dependent Calcium Channels ◽  
Whole Cell Recordings

N-type voltage-dependent calcium channels mediate the nicotinic enhancement of GABA release in chick brain. The role of voltage-dependent calcium channels (VDCCs) in the nicotinic acetylcholine receptor (nAChR)-mediated enhancement of spontaneous GABAergic inhibitory postsynaptic currents (IPSCs) was investigated in chick brain slices. Whole cell recordings of neurons in the lateral spiriform (SpL) and ventral lateral geniculate (LGNv) nuclei showed that cadmium chloride (CdCl2) blocked the carbachol-induced increase of spontaneous GABAergic IPSCs, indicating that VDCCs might be involved. To conclusively show a role for VDCCs, the presynaptic effect of carbachol on SpL and LGNv neurons was examined in the presence of selective blockers of VDCC subtypes. ω-Conotoxin GVIA, a selective antagonist of N-type channels, significantly reduced the nAChR-mediated enhancement of γ-aminobutyric acid (GABA) release in the SpL by 78% compared with control responses. Nifedipine, an L-type channel blocker, and ω-Agatoxin-TK, a P/Q-type channel blocker, did not inhibit the enhancement of GABAergic IPSCs. In the LGNv, ω-Conotoxin GVIA also significantly reduced the nAChR-mediated enhancement of GABA release by 71% from control values. Although ω-Agatoxin-TK did not block the nicotinic enhancement, L-type channel blockers showed complex effects on the nAChR-mediated enhancement. These results indicate that the nAChR-mediated enhancement of spontaneous GABAergic IPSCs requires activation of N-type channels in both the SpL and LGNv.

Effects of N- and L-type calcium channel antagonists on the responses of nociceptive spinal cord neurons to mechanical stimulation of the normal and the inflamed knee joint

1996 ◽  
Vol 76 (6) ◽  
pp. 3740-3749 ◽  
Author(s):  
V. Neugebauer ◽  
H. Vanegas ◽  
J. Nebe ◽  
P. Rumenapp ◽  
H. G. Schaible
Keyword(s):  
Spinal Cord ◽  
Knee Joint ◽  
Calcium Channels ◽  
Mechanical Stimulation ◽  
Topical Administration ◽  
Knee Joints ◽  
Spinal Cord Neurons ◽  
Inflammatory Conditions ◽  
Voltage Dependent ◽  
Voltage Dependent Calcium Channels

1. The present study addresses the involvement of voltage-dependent calcium channels of the N and L type in the spinal processing of innocuous and noxious input from the knee joint, both under normal conditions and under inflammatory conditions in which spinal cord neurons become hyperexcitable. In 30 anesthetized rats, extracellular recordings were performed from single dorsal horn neurons in segments 1–4 of the lumbar spinal cord. All neurons had receptive fields in the ipsilateral knee joint. In 22 rats, an inflammation was induced in the ipsilateral knee joint by kaolin and carrageenan 4–16 h before the recordings. The antagonist at N-type calcium channels, omega-conotoxin GVIA (omega-CTx GVIA), was administered topically in solution to the dorsal surface of the spinal cord at the appropriate spinal segments in 6 rats with normal joints and in 12 rats with inflamed knee joints. The antagonist at L-type channels, nimodipine, was administered topically in 5 rats with normal joints and in 11 rats with inflamed knee joints. In another five rats with inflamed joints, antagonists at L-type calcium channels (diltiazem and nimodipine) and omega-CTx GVIA were administered ionophoretically with multibarrel electrodes close to the neurons recorded. 2. The topical administration of omega-CTx GVIA to the spinal cord reduced the responses to both innocuous and noxious pressure applied to the knee joint in a sample of 11 neurons with input from the normal joint and in a sample of 16 neurons with input from the inflamed joint (hyperexcitable neurons). The responses were decreased to approximately 65% of the predrug values within administration times of 30 min. A similar reduction of the responses to innocuous and noxious pressure was observed when omega-CTx GVIA was administered ionophoretically to nine hyperexcitable neurons. In neurons with input from the normal or the inflamed knee joint, the administration of omega-CTx GVIA led also to a reduction of the responses to innocuous and noxious pressure applied to the noninflamed ankle joint. 3. The topical administration of nimodipine decreased the responses to innocuous and noxious pressure applied to the knee in a sample of 9 neurons with input from the normal joint and in a sample of 16 neurons with input from the inflamed knee joint (hyperexcitable neurons). Within administration times of 30 min, the responses were reduced to approximately 70% of the predrug values. In hyperexcitable neurons, the responses to innocuous and noxious pressure applied to the knee were also decreased during ionophoretic administration of nimodipine (6 neurons) and diltiazem (9 neurons). When the noninflamed ankle was stimulated, the responses to innocuous pressure were reduced neither in neurons with input from the normal knee nor in neurons with input from the inflamed knee, but the responses of hyperexcitable neurons to noxious pressure onto the ankle were reduced. The ionophoretic administration of the agonist at the L-type calcium channel, S(-)-Bay K 8644, enhanced the responses to mechanical stimulation of the knee joint in all 14 hyperexcitable neurons tested. The effect of S(-)-Bay K 8644 was counteracted by both diltiazem (in 6 of 6 neurons) and nimodipine (in 5 of 5 neurons). 4. These data show that antagonists at both the N- and the L-type voltage-dependent calcium channels influence the spinal processing of input from the knee joint. The data suggest, therefore, that voltage-dependent calcium calcium channels of both the N and the L type are important for the sensory functions of the spinal cord. They are involved in the spinal processing of nonnociceptive as well as nociceptive mechanosensory input from the joint, both under normal and inflammatory conditions. The present results show in particular that N- and L-type channels are likely to be involved in the generation of pain evoked by noxious mechanical stimulation in normal tissue as well as in the mechanical hyperalgesia that is usually pres

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