Blockade by ifenprodil of high voltage‐activated Ca²⁺ channels in rat and mouse cultured hippocampal pyramidal neurones: comparison with N‐methyl‐D‐aspartate receptor antagonist actions

Abstract

I The block by ifenprodil of voltage-activated Ca2+ channels was investigated on increases in intracellular free calcium concentration ([Ca2+]

Blockade by sigma site ligands of high voltage‐activated Ca2+ channels in rat and mouse cultured hippocampal pyramidal neurones

“…The whole-cell IB4 evoked in the present experiments is composed mainly of current flowing through nifedipine-resistant, (Fletcher et al, 1994) and ifenprodil (Church et al, 1994b). Rather, the data presented reflect the activity of the compounds as antagonists of the whole-cell IB4 flowing through the combination of HVA Ca2+ channels present in the neurones employed (see also Netzer et al, 1993;Biton et al, 1994 Figures 1 and 3,), suggesting in turn that their action occurs without influencing the kinetics of activation of HVA Ca2l channels.…”

“…In agreement with ffrench-Mullen & Rogawski (1992), we have also observed that dizocilpine is a very weak antagonist of whole-cell IB, (Fletcher, unpublished observations). The Ca2" channel blocking properties of the other compounds tested in the present experiments, with the exceptions of ifenprodil (Church et al, 1994b) and haloperidol (Fletcher et al, 1994), have not been previously reported, although it is of interest that the ifenprodil analogue, eliprodil (SL 82.0715) has recently been found to block the total IBI carried by L-and Ntype HVA Ca2" channels in rat cultured cortical neurones with an IC50 of 1.5 gM (Biton 1994). …”

“…ICso values for the compounds examined in the presence of nifedipine are presented in Table 1. With the single exception of ifenprodil (Church et al, 1994b), IC50 values were higher in the presence than in the absence of 10 pM nifedipine and, in some cases, approached those obtained for the reduction of the whole-cell IB. (see Table 1).…”

Increased contribution of NR2A subunit to synaptic NMDA receptors in developing rat cortical neurons

“…To investigate the nature of the native receptor composition at this developmental stage when synaptic connections are barely established, we had to electrically stimulate N_EPSCs (eN_EPSCs). This approach, however, raised the concern that blockade of voltage-gated Ca¥ conductances by NR1ÏNR2B antagonists Church, Fletcher, Baxter & MacDonald, 1994) A, selected sweeps illustrating mN_EPSCs in a visual cortical cell before (upper 4 traces), and during bath application with 100 ìÒ haloperidol (lower 4 traces). The mean mN_EPSC amplitudes were 15·5 ± 7·2 pA in control and 15·4 ± 5·7 pA with haloperidol (mean ± s.d., n = 164).…”

“…This approach allowed us to extend our investigation of synaptic NMDA receptors to rats at a very early postnatal age (P3-P5) in which no spontaneous synaptic events were detectable. For this investigation we used CP101,606, since both haloperidol and ifenprodil were shown to produce blockade of voltage-gated Ca¥ conductances Church et al 1994) and thereby elicit presynaptic effects. The possibility that the maximal CP101,606 concentration used in our experiments produced presynaptic actions was ruled out by studying its effects on AMPA receptor-mediated EPSCs.…”