125 Distribution of P-type, voltage-dependent calcium channels in mouse brain:A histochemical study using a biotinylated channel blocker, peptide toxin ω-aga IV A

Ifenprodil is a selective blocker of NMDA receptors that are heterodimers composed of GluN1/GluN2B subunits. This pharmacological profile has been extensively used to test the role of GluN2B-containing NMDA receptors in learning and memory formation. However, ifenprodil has also been reported to have actions at a number of other receptors, including high voltage-activated calcium channels. Here we show that, in the basolateral amygdala, ifenprodil dose dependently blocks excitatory transmission to principal neurons by a presynaptic mechanism. This action of ifenprodil has an IC50 of ∼10 μM and is fully occluded by the P/Q type calcium channel blocker ω-agatoxin. We conclude that ifenprodil reduces synaptic transmission in the basolateral amygdala by partially blocking P-type voltage-dependent calcium channels.

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

Journal of Neurophysiology ◽

10.1152/jn.1999.81.2.447 ◽

1999 ◽

Vol 81 (2) ◽

pp. 447-454 ◽

Cited By ~ 24

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.

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Voltage-Dependent Inhibition of N- and P-Type Calcium Channels by the Peptide Toxin ω-Grammotoxin-SIA

Molecular Pharmacology ◽

10.1124/mol.52.6.1095 ◽

1997 ◽

Vol 52 (6) ◽

pp. 1095-1104 ◽

Cited By ~ 53

Author(s):

Stefan I. McDonough ◽

Richard A. Lampe ◽

Richard A. Keith ◽

Bruce P. Bean

Keyword(s):

Calcium Channels ◽

Voltage Dependent ◽

Dependent Inhibition ◽

Peptide Toxin ◽

P Type

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Agatoxin-IVA-Sensitive Calcium Channels Mediate the Presynaptic and Postsynaptic Nicotinic Activation of Cardiac Vagal Neurons

Journal of Neurophysiology ◽

10.1152/jn.2001.85.1.164 ◽

2001 ◽

Vol 85 (1) ◽

pp. 164-168 ◽

Cited By ~ 15

Author(s):

Jijiang Wang ◽

Mustapha Irnaten ◽

David Mendelowitz

Keyword(s):

Calcium Channels ◽

Calcium Channel ◽

Calcium Channel Blocker ◽

Channel Blocker ◽

Patch Clamp Technique ◽

Current Increase ◽

Inward Current ◽

Voltage Dependent Calcium Channel ◽

Voltage Dependent ◽

Voltage Dependent Calcium Channels

Whole cell currents and miniature glutamatergic synaptic events (minis) were recorded in vitro from cardiac vagal neurons in the nucleus ambiguus using the patch-clamp technique. We examined whether voltage-dependent calcium channels were involved in the nicotinic excitation of cardiac vagal neurons. Nicotine evoked an inward current, increase in mini amplitude, and increase in mini frequency in cardiac vagal neurons. These responses were inhibited by the nonselective voltage-dependent calcium channel blocker Cd (100 μM). The P-type voltage-dependent calcium channel blocker agatoxin IVA (100 nM) abolished the nicotine-evoked responses. Nimodipine (2 μM), an antagonist of L-type calcium channels, inhibited the increase in mini amplitude and frequency but did not block the ligand gated inward current. The N- and Q-type voltage-dependent calcium channel antagonists conotoxin GVIA (1 μM) and conotoxin MVIIC (5 μM) had no effect. We conclude that the presynaptic and postsynaptic facilitation of glutamatergic neurotransmission to cardiac vagal neurons by nicotine involves activation of agatoxin-IVA-sensitive and possibly L-type voltage-dependent calcium channels. The postsynaptic inward current elicited by nicotine is dependent on activation of agatoxin-IVA-sensitive voltage-dependent calcium channels.

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