Ifenprodil reduces excitatory synaptic transmission by blocking presynaptic P/Q type calcium channels

2012 ◽  
Vol 107 (6) ◽  
pp. 1571-1575 ◽  
Author(s):  
Andrew J. Delaney ◽  
John M. Power ◽  
Pankaj Sah
Keyword(s):  
Calcium Channels ◽  
Synaptic Transmission ◽  
Nmda Receptors ◽  
Basolateral Amygdala ◽  
Excitatory Transmission ◽  
Voltage Dependent ◽  
Voltage Dependent Calcium Channels ◽  
P Type ◽  
Selective Blocker

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.

The role of voltage-dependent calcium channels in angiotensin-stmulated glomerulosa cells

1996 ◽  
Vol 22 (4) ◽  
pp. 569-576 ◽  
Author(s):  
A. Spät ◽  
T. Rohács ◽  
A. Horváth ◽  
G Y. Szabadkai ◽  
P. Enyedi
Keyword(s):  
Calcium Channels ◽  
Voltage Dependent ◽  
Voltage Dependent Calcium Channels ◽  
Glomerulosa Cells

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.

NMDA-Receptor-Dependent Synaptic Activation of Voltage-Dependent Calcium Channels in Basolateral Amygdala

2000 ◽  
Vol 83 (2) ◽  
pp. 685-692 ◽  
Author(s):  
Jeffrey L. Calton ◽  
Maeng-Hee Kang ◽  
Wilkie A. Wilson ◽  
Scott D. Moore
Keyword(s):  
Nmda Receptor ◽  
Calcium Channels ◽  
Basolateral Amygdala ◽  
Pyramidal Cells ◽  
Activation Threshold ◽  
Afferent Stimulus ◽  
Voltage Dependent ◽  
Nmda Glutamate Receptors ◽  
Voltage Dependent Calcium Channels ◽  
Cell Current

Afferent stimulation of pyramidal cells in the basolateral amygdala produced mixed excitatory postsynaptic potentials (EPSPs) mediated by N-methyl-d-aspartate (NMDA) and non-NMDA glutamate receptors during whole cell current-clamp recordings. In the presence of GABAA receptor blockade, the mixed EPSPs recruited a large “all-or-none” depolarizing event. This recruited event was voltage dependent and had a distinct activation threshold. An analogous phenomenon elicited by exogenous glutamate in the presence of tetrodotoxin (TTX) was blocked by Cd2+, suggesting that the event was a Ca2+ spike. Selective glutamatergic blockade revealed that these Ca2+ spikes were recruited readily by single afferent stimulus pulses that elicited NMDA EPSPs. In contrast, non-NMDA EPSPs induced by single stimuli failed to elicit the Ca2+ spike even at maximal stimulus intensities although these non-NMDA EPSPs depolarized the soma more effectively than mixed EPSPs. Elongation of non-NMDA EPSPs by cyclothiazide or brief trains of stimulation were also unable to elicit the Ca2+ spike. Blockade of K+ channels with intracellular Cs+enabled single non-NMDA EPSPs to activate the Ca2+ spike. The finding that voltage-dependent calcium channels are activated preferentially by NMDA-receptor-mediated EPSPs provides a mechanism for NMDA-receptor-dependent plasticity independent of Ca2+influx through the NMDA receptor.

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